T h e 2 0 1 4 ... C A R d i o vA s C u l... i n s T i T u T e ...

T h e 2 0 1 4 A n n u a l R e p o rt
C ar d i o v a s c u l ar r e s e arc h
Institute of vermont
T
he Cardiovascular Research Institute of
Vermont is dedicated to reducing the
incidence, morbidity, and mortality of heart
and vascular diseases through improving
prevention, diagnosis, and treatment.
By fostering collaborations among
departments at The University of Vermont
and The University of Vermont Medical
Center, the Cardiovascular Research
Institute of Vermont encourages the critical
thinking that challenges assumptions and
promotes excellence in clinical practice.
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Message from the Director
The University of Vermont (UVM) and The University of Vermont Medical Center
have a tradition of excellence in cardiovascular research—this report highlights
important accomplishments in 2014.
The Cardiovascular Research Institute of Vermont (CVRI) is broadly inclusive of all
who engage in cardiovascular research at UVM and its Medical Center. Our mission is
to foster cardiovascular research by supporting career development and by spotlighting
outstanding accomplishments.
David J. Schneider, M.D., F.A.C.C., F.A.H.A
Director
Cardiovascular Research
Institute of Vermont
Professor of Medicine
University of Vermont College of Medicine
Director of Cardiovascular Services
University of Vermont Health Network
Designated Distinguished Investigators of the CVRI highlight the legacy of cardiovascular
research. Career development is augmented in multiple ways, including an Early Career
Advisory Committee that is charged with guiding CVRI activity to support career
development; travel awards to assist early career investigators so they may present research
findings at scientific meetings; and invited speakers who enhance collaboration, stimulate
new discoveries, and interact directly with early career investigators to inspire commitment
to cardiovascular research.
Progress toward the ultimate goal, improving care of patients with cardiovascular
disease, is demonstrated by the many publications in cardiovascular research authored by
investigators at our academic medical center. Much of this research was made possible by
extramural funding for scientific discovery.
As you read through these pages, I trust you will join me in appreciating the depth and
breadth of cardiovascular research and in applauding the commitment of our investigators
who continuously strive for excellence.
Contents
Board of DIRECTORS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Leadership council . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
cardiovascular research NEWS. . . . . . . . . . . . . . . . . . . . . . . . . . . 4
The Next Generation: Early career advisory committee . . . . 6
The Next Generation: Travel Awards. . . . . . . . . . . . . . . . . . . . . . . 8
distinguished investigators. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Scholarly Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
research funding: Highlights. . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
research Publications: A sampling . . . . . . . . . . . . . . . . . . . . . . . 18
In Memory of Burton E. Sobel, M.D.. . . . . . . . . . . . . . . . . . . . . . . . 24
Contact. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
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a n n ua l
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Board of Directors
David J. Schneider, M.D., F.A.C.C., F.A.H.A., Director
Professor of Medicine, University of Vermont College of Medicine
Director of Cardiovascular Services, University of Vermont Health Network
Director, Cardiovascular Research Institute of Vermont
Dr. Schneider’s roles at the UVM Health Network and the Cardiovascular
Research Institute provide him the opportunity to translate scientific
advances into improved care of patients. His research focuses on
thrombosis, platelet function, and fibrinolysis as they relate to
atherosclerotic cardiovascular disease. His research efforts include the
development of anti-thrombotic agents and novel methods to assess the
risk of thrombosis and bleeding.
From left: Drs. Schneider, Dauerman, Cipolla, Warshaw, Nelson, Bernstein
and Cushman.
Harold L. Dauerman, M.D., F.A.C.C.
Professor of Medicine, Division of Cardiovascular Medicine, University of
Vermont College of Medicine; Interventional Cardiologist, University of
Vermont Medical Center
Ira Bernstein, M.D.
Professor and John Van Sicklen Maeck Chair of Obstetrics, Gynecology &
Reproductive Sciences, University of Vermont College of Medicine; Medical
Director of Women’s Services, University of Vermont Medical Center
Dr. Dauerman’s research focuses on high risk atherosclerotic coronary
syndromes and structural heart disease. He has investigated acute myocardial
infarction pathophysiology with highly sensitive intracoronary imaging devices
and applied systems-based approaches to optimize heart attack patient care; he
has helped develop minimally invasive technologies to treat patients with aortic
valve disease. He served as vice-chair of the American Heart Association Mission
Lifeline program and is the Editor in Chief of Coronary Artery Disease.
Dr. Bernstein served as Senior Associate Dean for Research at the UVM
College of Medicine from 2009-2014, and was Director of Maternal Fetal
Medicine and its fellowship program from 2003-2009. His research examines
human integrative cardiovascular physiology and he has been funded from
NIH for a series of projects examining pre-pregnancy determinants of
preeclampsia. Dr. Bernstein has served on several study sections at NIH,
including two years as the chair of Pregnancy and Neonatology.
Marilyn J. Cipolla, Ph.D., F.A.H.A.
Professor of Neurological Sciences, University of Vermont College of Medicine
Mark T. Nelson, Ph.D., F.A.H.A.
University Distinguished Professor and Chair of Pharmacology,
University of Vermont College of Medicine
Mary Cushman, M.D., M.Sc., F.A.H.A.
Professor of Medicine, Division of Hematology/Oncology, University
of Vermont College of Medicine; Director, Thrombosis and Hemostasis
Program, University of Vermont Medical Center
David M. Warshaw, Ph.D., F.A.H.A.
Professor and Chair of Molecular Physiology & Biophysics, University of
Vermont College of Medicine
Dr. Nelson’s goal is to understand the control of smooth muscle and endothelial
cell function by ion and calcium signaling. A major focus is to understand the
control of brain microcirculation in health and small vessel disease. Research
approaches cover the spectrum from molecular, cellular, intact tissue, whole
organ and in vivo, and a number of genetic mouse models are used to unravel
the control mechanisms. Dr. Nelson is internationally recognized for his
cutting edge research.
Dr. Cipolla’s research focuses on cerebral hemodynamics and cerebrovascular
function under normal and pathologic conditions, including ischemic stroke
and preeclampsia. Internationally recognized for her work, she is scientific
advisor to the NIH and WHO and past President of the Perinatal Research
Society. She is a Fellow and Established Investigator of the AHA and was
named University Scholar in 2015.
Dr. Warshaw’s research focuses on the structure and function of cardiac muscle
proteins in normal and failing hearts. Genetic mutations to the tiny protein
molecular motors that power the heart are the leading cause of sudden death in
young athletes. He is an Established Investigator and Fellow of the American
Heart Association. He has organized numerous international conferences and
symposia, and was a Scientific Advisor for the NIH Nanomedicine Initiative.
Dr. Cushman studies causes of cardiovascular-related diseases including
heart disease, stroke, cognitive impairment and venous thrombosis. She
uses biomarkers and genetic data from large epidemiologic studies where
her lab serves as biorepository and analysis lab, and has authored over 400
publications. She is a Board Director of the American Heart Association and
is Senior Guest Editor of Circulation.
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Leadership Council
Members of the Cardiovascular Leadership Council serve as ambassadors for the Cardiovascular Research Institute
of Vermont (CVRI), its Board of Directors, Investigators and Faculty, in the overall effort to educate and engage
Vermonters and the broader community in support of cardiovascular medicine.
Mary Evslin is co-founder of NG Advantage LLC,
a Vermont-based company that delivers natural gas to
large industrial plants not on a gas pipeline. Previously,
she was a founder of Marketing and Customer Success
at ITXC, where she developed and led the company’s
global marketing efforts from start-up through IPO
and secondary offering. Earlier in her career she
worked for then-U.S. Representative Jim Jeffords. She
is on the Board of Trustees of Champlain College and the Vermont/New
Hampshire Chapter of the American Red Cross, and was the first chair of
the Board of Directors of the Vermont Telecommunications Authority.
Mary lives in Stowe with her husband, Tom.
Mark Ray is the Director of Public Relations at
KSV, a Burlington marketing communications firm.
A graduate of Middlebury College, he honed his
skills in NYC at three top PR firms before returning
to Vermont in 1994. In 2001, Mark co-founded
an annual event in memory of his father, a cyclist
who died of heart disease, and has raised over
$120,000 for heart disease research and education.
Mark served as vice chair of the Make-A-Wish Foundation’s Vermont
board in 2013, and has also served on the boards of the American
Heart Association in Vermont and the Middlebury College Alumni
Association. Mark lives with his wife and two children in Shelburne.
Peter Gibbs is a Vice President at Engineering
Ventures PC, a civil and structural engineering
firm in Burlington. Previously, he owned his own
engineering firm based in Westport, N.Y., and has
been a practicing site and civil engineer for over
30 years. Peter holds a Master of Engineering from
Rensselaer Polytechnic Institute, and Bachelor of
Science degrees in both Ocean Engineering and
Civil Engineering from the Florida Institute of Technology. He is a
member of the Construction Specification Institute, a volunteer with
Engineers Without Borders, and a licensed U.S. Coast Guard Captain.
Peter and his wife Lauren reside in Shelburne.
Patrick Robins is founder and chairman of The
SymQuest Group, Inc., a regional technology services
company. Previously, Pat was Chairman and CEO of
McAuliffe, Inc. A graduate of St. Michael’s College
and the Tuck School of Business at Dartmouth, Pat
serves as a Director at Merchants Bancshares, is a
managing member of Sideronics LLC, and Director
of Butternut Mountain Farms, a national distributor
of maple products. He holds board positions on the Downtown
Burlington Development Corp., the VNA, Cynosure, Inc., the UVM
Medical Center, the Vermont Chamber of Commerce, and the Vermont
Land Trust. Pat and his wife, Lisa Schamberg, reside in Burlington.
Paul Millman is a founder and president of
Chroma Technology Corp., one of the most
important suppliers of optical filters and mirrors to
the world’s biotech industry. He is a graduate of the
New School and the Antioch New England Graduate
School and serves as director of the Vermont Business
Roundtable and Valley Net. He is on the Steering
Committee of ReThink Health in the Upper Valley
and president of the Westminster (Vermont) Fire and Rescue Association.
He is also a former director of Vermont Business for Social Responsibility
and former chair of the Vermont Employee-Ownership Center. He lives
in Westminster with his partner Wendy Cross.
Glen Wright is a certified public accountant, serving
as Managing Partner at KPMG LLP in Burlington
until 2002. Since then, he has continued his work
as a business and tax consultant in Burlington and
Reddick, Florida. Glen is Chairman of the Board of
Cynosure, Inc., whose mission is to provide financial
support for economic development in Chittenden
County through investment and management of
real estate projects. He has been a board member of the Flynn Theatre for
the Performing Arts, the Vermont Business Roundtable, the YMCA, the
UVM Medical Center Foundation and Chittenden Bank. Glen and his
wife Rosemarie, divide their time between South Hero and Florida.
www . uvm . edu / medicine / cvri
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Cardiovascular Research News
Promising New Treatment for Heart Rhythm Disorder
C
ardiologist and heart rhythm specialist
Peter Spector, M.D., is on a mission to
improve the cure rate for a form of the most
common heart rhythm disorder – atrial
fibrillation (AF) – and has already earned a
patent as he works towards this goal.
Roughly six to eight million cases of AF
exist in the U.S., but despite its prevalence,
medications only work in about 45 percent of
patients. An alternative to medication exists;
a procedure – called catheter ablation – is
effective in about 75 percent of patients with
intermittent AF, but the technique works
poorly in the majority of AF patients, who
suffer from a chronic form of the condition.
Spector’s three-year project – funded by
a $1 million grant from Vermont residents
Tom and Mary Evslin after Mr. Evslin was
treated for a heart condition at The University
of Vermont Medical Center – has yielded
innovative technology that offers a potential
new approach to catheter ablation of AF and
led to creation of an impressive intellectual
property portfolio covering the catheters,
signal processing algorithms and other aspects
of his research. He was awarded the first of
these U.S. patents in November 2014, and as
of January 2015, a second patent application
has been allowed.
Through all of these efforts, Spector and
colleagues hope to help the many patients
suffering from chronic AF to maintain a
regular heart rhythm, thus reducing their
risk of stroke and providing them with a
significantly higher quality of life.
“If our therapy is even 10 percent more
effective, it will help an enormous number of
people,” says Spector.
SPARK-VT Awards Support Innovation
S
PARK-VT, launched at UVM in 2012, brings the experience and insight of a panel
of distinguished and successful entrepreneurs to the critical evaluation of promising
innovative applications of new knowledge. Those adjudged to be most meritorious receive
start-up funding and milestone evaluation by the panel. In 2014, UVM Associate Professor
of Medicine Jeffrey Spees, Ph.D., earned a SPARK-VT award for his research on Cell-Kro, a
grafting agent composed of insulin and a peptide derived from Connective Tissue Growth
Factor. Cell-Kro has been shown in early studies to improve the adhesion, proliferation,
survival, and migration of cardiac stem cells grafted to a heart injured from a heart attack. In
2013, Associate Professor of Medicine Markus Meyer, M.D., earned an award for his project
to develop a fast and inexpensive way to test for heart function: A simple device to administer
a small dose of nitrogen to a patient and time its flow through the body. Meyer completed
follow-up studies on the heart function monitor, created a startup company to support his
venture, and submitted a Small Business Innovation Research (SBIR) grant.
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Translating Groundbreaking Cardiovascular
Research Into Improved Regional Care
A
CVRI Supports AHA
Go Red for Women
T
he American Heart Association’s
Vermont Go Red for Women
Luncheon attracts 500 attendees
each year to the organization’s Heart
Month event held in Burlington every
February. The University of Vermont
College of Medicine, University
of Vermont Medical Center and
Cardiovascular Research Institute of
Vermont co-sponsor the event, which
includes a morning panel discussion,
silent auction, and luncheon keynote
and survivor presentations. UVM
Professor of Surgery and Cardiothoracic
Surgeon Frank Ittleman, M.D. (shown
above), was named Vermont’s 2014
recipient of the Crystal Heart Award,
which recognizes an individual who
has contributed to the mission of the
American Heart Association and
American Stroke Association. Vermont
AHA Board Chair Mary Cushman,
M.D., M.Sc., presented the award to
Dr. Ittleman.
procedure tested during a clinical trial at the University of Vermont to replace heart valves using
catheters instead of open heart surgery received approval in July 2014 from the Food and Drug
Administration for use in two categories of patients. The American Heart Association and the
American College of Cardiology have also added Transcatheter Aortic Valve Replacement (TAVR)
to their guidelines.
Patients from Vermont and northern New York who had failing heart valves but could not
tolerate open heart surgery (the current standard of care for valve replacement) or were at high
risk for complications or death during surgery were among the first in the country to receive this
groundbreaking treatment. The UVM Medical Center was one of only 45 sites in the trial and has
enrolled over 100 regional patients in research trials and registries studying and developing TAVR.
During TAVR, an artificial valve is placed on a catheter and is advanced to the heart from a
vessel in the leg or chest, similar to what happens when inserting a stent. When the new valve is
released, it pushes the diseased valve out of the way and begins functioning immediately.
“TAVR is truly a lifesaving treatment and we’re very pleased our heart team was involved in
determining its effectiveness,” said clinical investigator Harry Dauerman, M.D. “It’s a great example
of the value of having an academic medical center in our region – we not only have the expertise and
resources to deliver the most advanced treatments, but we are also involved in developing them.”
UVM has continued to take the lead in enrollment of high risk, off label patients in an ongoing
national TAVR research registry and has now developed one of the highest volume clinical TAVR
programs in our region.
The Totman Medical Research Fund
The Totman Medical Research Trust supports an interdepartmental, highly interactive research group focused on key
aspects of brain artery function from molecules to clinical applications. The program is housed in the Department
of Pharmacology, under the supervision of University Distinguished Professor and Chair Mark T. Nelson, Ph.D., who
hosts an annual session with Fund leaders and researchers (above, in 2014) to hear presentations and share ideas.
The Fund was established through the generosity of Ray Totman, a businessman from Malone, New York. After his
death in 1988, a gift from his estate established the Ray W. Totman and Ildah Totman Medical Research Fund, to be
used for scientific and medical research concerning Ischemic Cerebrovascular Disease.
www . uvm . edu / medicine / cvri
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The Next Generation:
Early Career Advisory Committee
W
Sobel Visiting Professor Joseph Loscalzo, M.D., Ph.D., Chair of Medicine at Brigham &
Women’s Hospital and Editor-in-Chief of Circulation, talks with Early Career scientists at
the “Master’s Tea” during his visit to campus in March 2015.
“You want your trainees to have the opportunity to
meet people who are leaders in their field—it teaches
them how to interact with scientists
outside our institution. This can often
initiate new collaborations, inspire new
projects, and develop new mentors.”
Mary Cushman, M.D., M.Sc.
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ith travel awards, research seminars,
and an Early Career Advisory
Committee available to them, junior
investigators who are affiliated with the
Cardiovascular Research Institute of
Vermont (CVRI) have plenty of rich
opportunities at their disposal.
The Early Career Advisory Committee
is at the heart of the CVRI support of
the future of cardiovascular research and
medicine. Its eight members, selected by
application to the CVRI Board of Directors,
represent multiple of departments and levels
of expertise—they range from fourth-year
medical students to early career faculty
members in Microbiology, Molecular
Genetics and Obstetrics, Gynecology and
Reproductive Sciences. In addition to
coordinating events such as Journal Clubs for
their peers, committee members participate
in the planning of the Visiting Professorships
and report regularly to the CVRI Board on
issues faced by their early career colleagues.
The committee is shepherded by Mary
Cushman, M.D., M.Sc., director of the
Thrombosis and Hemostasis Program,
professor of medicine in the Hematology/
Oncology Division, professor of pathology,
and a member of the CVRI Board for whom
mentoring has long been a professional
passion. She says that inviting early career
individuals to dinners with visitors and to
professional development events where they
are welcome to present their work and get
feedback, is important on several levels.
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From left to right: Sean McMahon, M.D., Abbie Johnson, Ph.D., Kara Klingman Landry, Kelley McLean, M.D., Michael Previs, Ph.D., Dawei Li, Ph.D.,
Mary Cushman, M.D., M.Sc., Nels Olson, Ph.D., and Patrick Hohl, D.O.
2014-15 Early Career Advisory Committee
Patrick Hohl, D.O.
1st year fellow
Medicine – Cardiology
Kelley McLean, M.D.
Assistant Professor
Obstetrics, Gynecology and Reproductive Sciences
Abbie Johnson, Ph.D.
Postdoctoral Associate
Neurological Sciences
Sean McMahon, M.D.
1st year fellow
Medicine – Cardiology
Kara Klingman Landry, B.A.
4th year medical student
UVM College of Medicine
Nels Olson, Ph.D.
Postdoctoral Fellow
Pathology and Laboratory Medicine
Dawei Li, Ph.D.
Assistant Professor
Microbiology and Molecular Genetics
Michael Previs, Ph.D.
Assistant Professor
Molecular Physiology and Biophysics
www . uvm . edu / medicine / cvri
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The Next Generation: Travel Awards
Travel awards were established to cover educational travel costs for anyone early in his or her career who is a primary
presenting author of an abstract at a regional or national meeting. It’s an honor, and it also means that money that would
otherwise have to be used to pay for them to participate can be earmarked for direct research costs instead. Since July
2014, thirteen $2,000 awards have been made, sending assistant professors, postdoctoral fellows, residents in internal
medicine, and graduate and medical students to regional, national and international meetings.
American Heart Association
Epidemiology, Prevention, Lifestyle
and Cardiometabolic Health
2015 Scientific Sessions
American Society of Nuclear Cardiology
2014 Annual Scientific Sessions
Boston, MA – September 18-21, 2014
Sean R. McMahon, M.D.
Internal Medicine Resident, Department of Medicine
Poster: Increased use of regadenoson in patients with abnormal
troponin I in the era of sensitive troponin assays
Baltimore, MD – March 3-6, 2015
Kristine Alexander, Ph.D., M.C.R.
Postdoctoral Fellow, Department of Medicine
Poster: Nonalcoholic fatty liver disease (NAFLD) and risk of incident
cognitive impairment
American Heart Association
Scientific Sessions 2014
Markus Degirmenci, M.D.
Internal Medicine Resident, Department of Medicine
Poster: Dehydroepiandrosterone (DHEAS) and risk of stroke in
black and white Americans: The REasons for Geographic And Racial
Differences in Stroke (REGARDS) cohort
Chicago, IL – November 7-11, 2014
Zubin Agarwal, M.D., M.P.H.
Internal Medicine Resident, Department of Medicine
Poster: Galectin-3 and risk of stroke: The REasons for Geographic And
Racial Differences in Stroke (REGARDS) cohort
Peter Durda
Graduate Student, Department of Pathology
Poster: Circulating soluble CD163 and risk of cardiovascular disease
and all-cause mortality in older persons: the Cardiovascular Heart
Study (CHS)
Biophysical Society
59th Annual Meeting
Baltimore, MD – February 7-11, 2015
Michael J. Previs, Ph.D.
Assistant Professor, Department of Molecular Physiology and Biophysics
Poster and Oral: Myosin-binding protein C corrects an intrinsic nonuniformity in cardiac excitation-contraction coupling
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Kara Klingman Landry
UVM Medical Student, Class of 2015
Poster: Association of stroke risk biomarkers with stroke symptoms:
the REasons for Geographic And Racial Differences in Stroke
(REGARDS) cohort
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Society for Reproductive Investigation
62nd Annual Scientific Meeting
San Francisco, CA – March 25-28, 2015
Erin Morris, M.D.
Fellow, Department of Obstetrics, Gynecology, and Reproductive Sciences
3 Posters: Prepregnancy blood pressure and history of first trimester
loss contribute to birth weight and placental weight; Cerebral blood
flow changes over pregnancy in women with a history of HELLP
syndrome and those with prior preeclampsia; and Persistence of
pregnancy-induced maternal uterine vascular remodeling in rodents
Lindsay Howe, B.S.
Graduate Student, Department of Obstetrics, Gynecology, and
Reproductive Sciences
Poster: Obesity, body fat distribution and cardiovascular function in
young nulliparous women
Carole McBride
Graduate Student, Department of Obstetrics, Gynecology, and
Reproductive Sciences
3 Posters: Factors influencing early pregnancy uterine arterial blood
flow and resistance index; Maternal hypertension and major morbidity
in infants born 22 to 29 weeks gestation; and Physical fitness and
cardiovascular phenotype in young women
Experimental Biology 2015
Boston, MA – March 28-April 1, 2015
Thomas A. Longden, Ph.D.
Postdoctoral Fellow, Department of Pharmacology
Poster: Unique ion channel property of brain capillary
endothelial cells
Yao Li
Graduate Student, Department of Pharmacology
Poster: Rho kinase regulates myogenic depolarization of cerebral
parenchymal arterioles
International Society for Stem Cell Research
2015 Annual Meeting
Stockholm, Sweden – June 24-17, 2015
Krithika Rao
Graduate Student, Department of Medicine
Oral: CTGF-D4/LRP6 signaling promotes adult epicardial cell grafts
after MI
“The ability to underwrite expenses
early in a young researcher’s career
is crucial to his or her
success, and we’re
here to support our
junior investigators.”
Harold Dauerman, M.D.
www
www. .uvm
uvm. .edu
edu//medicine
medicine//cvri
cvri
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Distinguished Investigators
The Cardiovascular Research Institute of Vermont (CVRI) recognized six University of
Vermont faculty in 2014 as Distinguished Investigators, recognizing the long-term high
impact of their work in cardiovascular research. Appointed for a period of five years, the
inaugural group was celebrated in April 2014.
Russell Tracy, Ph.D.
Professor of Pathology
Dr. Tracy’s Laboratory for Clinical Biochemistry
Research was the clearinghouse for the massive
Exome Sequencing Project sponsored by NIH’s
National Heart, Lung and Blood Institute (NHLBI).
His own research was an integral part of the ESP’s
HeartGO consortium, as well as the NHLBI’s
Cardiovascular Heart Study and the National Center
for Biotechnology Information’s Multi-Ethnic Study of
Atherosclerosis. Tracy, interim senior associate dean for
research, LCBR director, and 2009 University Scholar,
is exploring genetic risk factors related to myocardial
infarction and atherosclerosis, among other diseases.
George Osol, Ph.D.
Professor of Obstetrics, Gynecology and
Reproductive Sciences
Dr. Osol’s research is focused on vascular adaptations
in pregnancy—in particular, the process of uterine
artery remodeling in both normal and hypertensive
pregnancies. Uterine vasculature undergoes more
expansion during gestation than any other blood
vessel in the human body ever does; insufficient
remodeling or excessive constriction can result in
preeclampsia and intrauterine growth restriction.
Osol is program director for the NIH Center
of Excellence in Women’s Reproductive Health
Research and a 2010 University Scholar. His work
has received NIH support for more than 25 years.
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Kathleen M. Trybus, Ph.D.
Professor of Molecular Physiology and Biophysics
Joseph E. Brayden, Ph.D.
Professor of Pharmacology
Dr. Brayden’s laboratory investigates the ionic mechanisms of
vasoconstriction, vasodilation, and communication between
endothelial and smooth muscle cells in cerebral arterioles—with a
focus on signaling pathways involved in cellular calcium regulation—
using electrophysiological, optical, and molecular techniques.
Brayden is also working to identify the roles of vascular endothelium
and its many ion channels in cerebral and peripheral artery
vasodilator function, and is a pioneer in research on the electrical
properties of vascular smooth muscle.
Dr. Trybus is engaged in the
study of molecular motors
and their cargo. Specifically,
she has zeroed in on how
myosin activity is regulated,
and how it moves actin and
produces force. Trybus is also
interested in the mechanisms
that cause mutations in
smooth muscle actin to
result in vascular disease—
in particular, thoracic
aneurysms and coronary artery disease—by expressing homogenous
normal and mutant vertebrate actins in the baculovirus/insect cell
expression system, and has followed the polymerization of single actin
filaments in real time.
Martin M. LeWinter, M.D.
Professor of Medicine
Broadly, Dr. LeWinter has
trained his research eye on
myocardial and ventricular
functioning and remodeling
in cardiomyopathy and heart
failure. Specifically, he’s looking
at the mechanoenergetics of
the myocardium, diastolic
left ventricular function, and
the effect of diabetes and
hypertension on myocardial
function. LeWinter, a 2007 University Scholar, is director of the UVM
Medical Center’s Heart Failure Program and principal investigator of
a grant designating the University one of nine NIH-funded Regional
Clinical Centers for heart failure research.
Philip Ades, M.D.
Professor of Medicine
Dr. Ades’ father died of heart disease at a young age, and his own
work is dedicated to ensuring that others don’t suffer the same
fate. With a research and clinical spotlight on weight loss in obese
coronary patients, Ades, who is director of Cardiac Rehabilitation
and Prevention, teaches patients that exercise is medicine, but
everyone needs a specific dose. His research, which has had
consistent NIH funding since 1988, focuses on the treatment and
prevention of disability in older patients with coronary artery
disease and patients with chronic heart failure.
www . uvm . edu / medicine / cvri
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Scholarly Events
The Cardiovascular Research Institute of Vermont (CVRI) brings outstanding scientists in cardiovascular medicine to
The University of Vermont as Visiting Professors. These visits include a major lecture and a series of interactions with
trainees and junior investigators.
CVRI Visiting Professors
Sobel Visiting Professor
October 10, 2014
Honoring Burton E. Sobel, M.D., the Founding
Director of the CVRI.
Translational Stroke Research: A Personal Perspective
Marc Fisher, M.D., M.Sc.
Professor Emeritus of Neurology, University of Massachusetts
Editor-in-Chief of Stroke
March 26-27, 2015
November 7, 2014
Chair and Physician-in-Chief, Department
of Medicine, Brigham and Women’s Hospital;
Hersey Professor of the Theory and Practice of
Medicine, Harvard Medical School; Editor-inChief of Circulation
• Seminar: How to Write and Publish a Paper:
Lessons Learned as an Author, Mentor, and
Editor
• Grand Rounds: Systems Pathobiology and
Personalized Cardiovascular Medicine
• Master’s Tea and dinner with the Early Career
Advisory Committee
Peripheral Artery Disease: Clinical Insights and Contemporary
Treatments to Preserve Life and Limb
Mark Creager, M.D.
Professor of Medicine, Harvard Medical School; Senior Physician, Brigham
and Women’s Hospital; President-Elect of the American Heart Association
November 18, 2014
In Search of the Holy Grail: Where Next in Prediction of
Preeclampsia?
Leslie Myatt, Ph.D.
Professor of Obstetrics and Gynecology, Director of the Center for
Pregnancy and Newborn Research, University of Texas Health Science
Center San Antonio
March 5, 2015
Mitochondrial Dynamism and Heart Disease
Gerald Dorn, Ph.D.
Philip and Sima K. Needleman Professor and Associate Chair for
Translational Research, Department of Internal Medicine, and Director
of Center for Pharmacogenomics, Washington University
May 8, 2015
Heart Failure
Marvin Konstam, M.D.
Professor of Medicine, Tufts University; Chief Physician Executive,
The CardioVascular Center at Tufts Medical Center
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car diovascu l ar r e search i nstitute of ve r mont
The Inaugural Sobel Visiting Professor
Joseph Loscalzo, M.D., Ph.D.
Burton E. Sobel, M.D.
Joseph Loscalzo, M.D., Ph.D.
Alpert Visiting Professor
Honoring Norman Alpert, Ph.D., Professor and
Chair of the UVM Department of Molecular
Physiology and Biophysics from 1966 to 1995.
May 3-5, 2015
The Inaugural Alpert Visiting Professor
Leslie A. Leinwand, Ph.D.
Howard Hughes Medical Institute Professor of
Molecular, Cellular and Developmental Biology,
Chief Scientific Officer, BioFrontiers Institute,
University of Colorado Boulder
Events planned include a seminar “Translating
Python Biology to Mammalian Hearts,” and
Early Career Discussion Forum.
•
2 0 14 a n n u a l r e p o r t
Norman Alpert, Ph.D.
Patent Activity
New Patent Filed
Jeffrey L. Spees, Ph.D.
• Cell-Kro (C-terminal domain 4 of CTGF and Insulin)
Ongoing Patent Activity
Marilyn J. Cipolla, Ph.D.
• Methods of treating diseases associated with PPARγ
• Oxidized LDL as a biomarker for brain injury in preeclampsia
David J. Schneider, M.D.
• Compositions and methods for assaying platelet reactivity and
treatment selection
Peter Spector, M.D.
• Method and systems for optimizing detection and treatment
of atrial fibrillation
• Methods and systems for mapping cardiac fibrillation
• Methods and systems for optimizing lesion placement to
minimize and treat cardiac fibrillation
• Methods and systems for minimizing and treating cardiac
fibrillation
• Methods and systems for determining spatiotemporal
variability for mapping cardiac fibrillation
• Catheter systems and related methods for mapping,
minimizing and treating cardiac fibrillation
• Methods and systems for assessing cardiac fibrillogenicity
• An interactive tissue model for simulating the electrical
activity of excitable tissues
Companies Formed
selected scholarly
Presentations
Mary Cushman, M.D., M.Sc.
Clinical Roles for Thrombophilia Testing: the 4Ps Approach
Thrombosis and Hemostasis Summit of North America
April 2014; Chicago, IL
Saulius Butenas, Ph.D.
Activation, Activity and Inactivation of FVIII in FVIII Products
XXXI International Congress of the World Federation
of Hemophilia
May 2014; Melbourne, Australia
Kathleen E. Brummel-Ziedins, Ph.D.
Correlation of Bleeding and Thrombotic Phenotypes with Computational
Modeling of Thrombin Generation
2014 7th Symposium on Hemostasis:
Old System, New Players, New Directions
May 2014; Chapel Hill, NC
Harold L. Dauerman, M.D.
Chair of Programming for the Clinical Cardiology Council and Scientific
Sessions Programming Committee Member
2014 American Heart Association Annual
Scientific Sessions
November 2014; Chicago, IL
Marilyn J. Cipolla, Ph.D.
Targeting Parenchymal Arterioles for Treatment of
Acute Stroke
Brain Ischemia and Stroke (BIS) 2014 Conference
December 2014; Rome, Italy
Markus Meyer, M.D.
• SimMedTec, LLC
To develop a handheld circulation monitor
www . uvm . edu / medicine / cvri
13
Research Funding: Highlights
Understanding the causes and consequences of cardiovascular disease, from the molecule to the patient to
populations to policy, drives a robust research enterprise at the University of Vermont, and represents a significant
portion of the $81 million in funding received by the College of Medicine in 2014. Grant support comes from
Federal, State, Corporate and Non-Profit sources; a sampling of recent awards is presented below.
Government Funded Research:
NIH, NHLBI, DMRDP, and other related awards
NIH 13761
Systems Biology for Biological Responses to Severe Hemorrhage – UVM
Co-PI: Kenneth Mann, Ph.D. and Kathleen Brummel-Ziedins, Ph.D.
$1,503,734
Ad5.AC6 Gene Transfer for CHF: Use of
Intracoronary AC6 Gene Therapy to Improve
Symptomatic Heart Failure
Local PI: Matthew Watkins, M.D.
$26,000
HL-13-025
P01 HL095488-01
DMRDP
Analysis and Characterization of TraumaInduced Coagulopathy
Project 2 – The Role of Factor Xla in TIC
Saulius Butenas, Ph.D.
Project 6 – Analysis and Characterization of
Trauma-Induced Coagulopathy
PI: Kathleen Brummel-Ziedins, Ph.D.
$23,999,991
K08 HL096841
Calcium Signaling in the Cerebrovascular
Unit in Health and Disease
PI: Mark Nelson, Ph.D.
$11,447,202
P01 HL059408-11
Kathleen BrummelZiedins, Ph.D.
Regional and Racial Differences in Hemostasis
and Risk of Stroke and Heart Disease
PI: Neil Zakai, M.D.
$130,599
Cardiac Myosin Binding Protein-C: Molecular Mechanisms of
Actomyosin Modulation
PI: David Warshaw, Ph.D.
$10,274,400
P20 GM103644-01A1
Vermont Center for Behavior and Health
PI: Stephen Higgins, Ph.D.
$1,533,382
N01 HC95166
Multiethnic Study of Atherosclerosis (MESA)
II – Laboratory Center
PI: Russell Tracy, Ph.D.
$88,014
Matthew Watkins, M.D.
P50 DAO36114
Neil Zakai, M.D.
NIH – NICHD
Tobacco Centers of Regulatory Science
Local PI: Stephen Higgins, Ph.D.
$2,924,426
PPG Project 1
National Longitudinal Study of Adolescent Health – Wave V
Subcontract PI: Mary Cushman, M.D., M.Sc.
$110,102
Molecular Mechanisms of ACTA2 Missense Mutations
PI: Kathleen Trybus, Ph.D.
$1,952,220
NIH – NIEHS
PPG Project 2 P01 HL095488
Effects of Perfluoroaklyl Chemicals on Stroke Incidence and
Mortality Local
Subcontract PI: Mary Cushman, M.D., M.Sc.
$6,746
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Cav channels, TRP channels and vasomotor function in cerebral arterioles
PI: Joseph Brayden, Ph.D.
$1,362,000
•
2 0 14 a n n u a l r e p o r t
PPG Project 3: P01 HL095488-01
R01 HL089944
Cerebrovascular Function during Ischemia and Reperfusions
PI: Marilyn Cipolla, Ph.D.
$1,900,000
Advanced Glycated End-Products in Human Myocardium
PI: Martin M. LeWinter, M.D.
$50,000
PPG Project 4 P01 HL095488
R01 NS073815
Impact of SAH on parenchymal arterioles and neurovascular coupling
PI: George Wellman, Ph.D.
$1,205,000
R01 HL071944-05
Pre-pregnancy Phenotype and Predisposition to Preeclamplsia
PI: Ira Bernstein, M.D.
$1,881,250
R01 NS045940-10
The Role of the Blood-brain Barrier in Seizure during Pregnancy
and Preeclampsia
PI: Marilyn Cipolla, Ph.D.
$1,667,970
R01 HL059367
Epidemiology of Venous Thrombosis and Pulmonary Embolism
Local PI: Mary Cushman, M.D., M.Sc.
$205,334
R01 AG023629
Exceptional Survival: Trajectories to Function
Subcontract PI: Mary Cushman, M.D., M.Sc.
$36,230
R01
The Myofilament Basis of HFpEF
PI: Martin M. LeWinter, M.D.
$191,000
R01 HL121706-01A1
Regulation of Myoendothelial Function by Signaling Microdomains
in Hypertension
PI: Mark T. Nelson, Ph.D.
$1,923,375
Control of reactive astrocytes by Notch1 and Amyloid Precursor Protein
PI: Jeffrey Spees, Ph.D.
$219,000
R01 AG033547
Muscle Disuse and Contractile Dysfunction in
the Elderly
PI: Michael Toth, Ph.D.
$2,802,106
R01
Mutational Studies of Processive Myosin Motors
PI: Kathleen Trybus, Ph.D.
$1,747,810
Michael Toth, Ph.D.
U01 NS41588
Etiology of Geographic and Racial Differences in Stroke Mortality
Subcontract PI: Mary Cushman, M.D., M.Sc.
$1,030,957
U10 HL110342
NHLBI Heart Failure Research Network –
Vermont, New York and Quebec Regional Clinical Center
PI: Martin M. LeWinter, M.D.
$240,000
UM1 HL120877
Analysis and Characterization of Trauma-Induced Coagulopathy
PI: Kenneth Mann, Ph.D., and Mark T. Nelson, Ph.D. (Lead Project 12
and Co-I Project 1)
$23,769,600
www . uvm . edu / medicine / cvri
15
Research Funding: Highlights (continued)
Non-Profit Funded Research
American Heart Association
Coupled myosin Va motor communication during
cargo transport in vitro
PI: M. Yusuf Ali, Ph.D.
$308,000
Functional interaction between plateletderived
growth factor receptor-beta and cyclic-AMPdependent protein kinase A
PI: Paula Deming, Ph.D.
$308,000
Pathogenesis of Small Vessel Disease of the Brain
North American Coordinator: Mark T. Nelson, Ph.D.
$6,000,000 (5 years)
March of Dimes Foundation
Mechanical Control of Chromosome Geometry
PI: Jason Stumpff, Ph.D.
$82,500
Preeclampsia Foundation Vision Award
M. Yusuf Ali, Ph.D.
Hydrogen peroxide and age-related sympathetic nervous system dysregulation
PI: Benedek Erdos, Ph.D., M.D.
$308,000
Mechanisms of EGF receptor activation leading to decreased cerebral blood
flow after subarachnoid hemorrhage
PI: Masayo Koide, Ph.D.
$308,000
Hemodynamic Contributions to the Control of Neuronal Function
PI: Thomas Longden, Ph.D.
$47,000
Involvement of TRPM4 in pressure- and agonist-induced
vasoconstriction in the cerebral microcirculation
PI: Yao Li, B.S.
$46,000
The Role of The Blood-Brain Barrier in Seizure During Pregnancy and
Preeclampsia
PI: Abbie Johnson, B.S.
$46,000
16
Fondation Leducq
car diovascu l ar r e search i nstitute of ve r mont
The Role of Efflux Transporters on the Bloodbrain Barrier in Preventing Seizure During
Pregnancy
PI: Erica Hammer, M.D.
$25,000
Totman Medical Research Trust
Cerebrovascular Research
PI: Mark T. Nelson, Ph.D.
$150,000
Erica Hammer, M.D.
Industry Sponsored Research
Abbott Vascular
ABSORB 3: A randomized trial comparing a
fully bioresorbable drug eluting poly lactic acid
polymer coronary stent versus a permanent
everolimus eluting coronary stent
PI: Harold Dauerman, M.D.
$44,500
Baxter BioScience
Evaluation of B-domainless Factor VIII Products
PI: Saulius Butenas, Ph.D.
$399,824
•
2 0 14 a n n u a l r e p o r t
Saulius Butenas, Ph.D.
Boston Scientific
Prospective Randomized Evaluation of the WATCHMAN LAA Closure
Device In Patients with Atrial Fibrillation Versus Long Term Warfarin
Therapy (PREVAIL) and Continued Access to PREVAIL (CAP2)
PI: Daniel Lustgarten, M.D.
$66,000
diaDexus
Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Activity and the Risk
of Stroke, Coronary Heart Disease and Cognitive decline in REGARDS
PI: Mary Cushman, M.D., M.Sc.
$50,340
Medtronic
A Novel Treatment for Heart Failure with Preserved Ejection Fraction
PI: Markus Meyer, M.D.
$100,000
Attain Performa Quadripolar Lead Clinical Study
PI: Daniel Lustgarten, M.D.
$9,400
CoreValve® Expanded Use and Continued Access Transcatheter Aortic
Valve Replacement Registries
PI: Harold Dauerman, M.D.
$873,500 for 92 patients
CoreValve® Surgical Replacement and
Transcatheter Aortic Valve Implantation
(SURTAVI and Pivotal Randomized Trials)
PI: Harold Dauerman, M.D.
$273,400 for 26 patients
Pacing-induced Remodeling in a Swine Model
of Left Ventricular Hypertrophy II
PI: Markus Meyer, M.D.
$75,000
Pacing-induced Remodeling in a Swine Model of Left Ventricular
Hypertrophy III
PI: Markus Meyer, M.D.
$20,000
Product Performance Platform
PI: Robert Lobel , M.D.
$23,000
SIMPLICITY HTN-3: A randomized trial of renal denervation
versus maximal medical therapy for severe hypertension
PI: Harold Dauerman, M.D.
$100,000
Sanofi
Odyssey Outcome Trial
PI: Friederike Keating, M.D.
$56,000
St. Jude Medical
Quadripolar Pacing Post Approval Study
PI: Daniel Lustgarten, M.D.
$7,700
The Medicines Company
Transition from Cangrelor to Ticagrelor,
Prasugrel, and Clopidogrel
PI: David J. Schneider, M.D.
$136,800
Daniel Lustgarten, M.D.
Markus Meyer, M.D.
www . uvm . edu / medicine / cvri
17
Research Publications: A Sampling
Across our academic medical center campus, throughout the region, and around the world, teams of physicians and
scientists are dedicated to reducing the incidence, morbidity, and mortality of heart and vascular diseases through
improving prevention, diagnosis and treatment. We are pleased to present a sampling of publications from our
University of Vermont colleagues engaged across a wide range of cardiovascular research.
Heart/Muscle Function and Failure,
Heart Rhythm Disorders
Angerer H, Radermacher M, Mańkowska M, Steger M,
Zwicker K, Heide H, Wittig I, Brandt U, Zickermann
V. The LYR protein subunit NB4M/NDUFA6 of
mitochondrial complex I anchors an acyl carrier protein
and is essential for catalytic activity. Proc Natl Acad Sci U
S A. 2014 Apr 8;111(14):5207-12.
Callahan DM, Bedrin NG, Subramanian M, Berking
J, Ades PA, Toth MJ, Miller MS. Age-related structural
alterations in human skeletal muscle fibers and
mitochondria are associated with whole muscle size and
single fiber function. J Appl Physiol 116: 1582-1592, 2014.
Callahan DM, Miller MS, Sweeney AP, Tourville TW,
Slauterbeck JR, Savage PD, Maugan DW, Ades PA,
Beynnon BD, Toth MJ. Muscle disuse alters skeletal
muscle contractile function at the molecular and cellular
levels in older adult humans in a sex-specific manner. J
Physiol. 2014; 592:4555-73.
Hariharan, S., Kelm, R. J., Jr., and Strauch, A. R. (2014)
The Purα/Purβ single-strand DNA-binding proteins
attenuate smooth muscle actin gene transactivation in
myofibroblasts. J. Cell. Physiol. 229, 1256-1271.
Imazio M, Belli R, Beqaraj F, Giammaria M, Lestuzzi
C, Hoit B, LeWinter M, Spodick DH, Adler Y; DROP
Investigators. DRainage Or Pericardiocentesis alone
for recurrent nonmalignant, nonbacterial pericardial
effusions requiring intervention: rationale and design of
the DROP trial, a randomized, open-label, multicenter
study. J Cardiovasc Med (Hagerstown). 2014;15:510-4.
Leary PJ, Jenny NS, Barr RG, Bluemke DA, Harhay MO,
Heckbert SR, Kronmal RA, Lima JA, Mikacenic C, Tracy
RP, Kawut SM. Pentraxin-3 and the right ventricle: The
multi-ethnic study of atherosclerosis-right ventricle study.
Pulmonary Circ 2014;4(2):250-259.
LeWinter MM. Clinical practice. Acute pericarditis. N
Engl J Med. 2014;371:2410-6.
18
LeWinter C, Bland JM, Crouch S, Cleland JG, Doherty
P, LeWinter MM, Køber L, Hall AS, Gale CP. Impact
of aspirin and statins on long-term survival in patients
hospitalized with acute myocardial infarction complicated
by heart failure: an analysis of 1706 patients. Eur J Heart
Fail. 2014;16:95-102.
LeWinter MM, Granzier HL Cardiac titin and heart
disease. J Cardiovasc Pharmacol. 2014;63:207-12.
Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Schempp P,
Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott
SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller
J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN,
Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM,
DAPT Study Investigators. Twelve or 30 months of dual
antiplatelet therapy after drug-eluting stents. N Engl J
Med. 2014; 371:2155-66.
Meyer M, Bell SP, Sardana N, Zubarik R, LeWinter MM,
Dauerman HL. Esophageal assessments of left ventricular
filling pressures: A proof-of-concept study. Int J Crit Illn
Inj Sci 2014; 4:18-23.
Meyer M. Cardiac Atrophy. J Am Coll Cardiol. 2014;
64:38-40.
Mohammed SF, Borlaug BA, McNulty S, Lewis GD, Lin
G, Zakeri R, Semigran MJ, LeWinter M, Hernandez AF,
Braunwald E, Redfield MM. Resting ventricular-vascular
function and exercise capacity in heart failure with
preserved ejection fraction: a RELAX trial ancillary study.
Circ Heart Fail. 2014;7:580-9.
Spector. P and Habel N. Principles of Differential
Diagnostic Pacing Maneuvers: Serial vs. Parallel
Conduction. Pacing Clin Electrophysiol. 2014 May 27.
Subramanian M, Hunt AL, Petrucci GA, Chen Z,
Hendley ED, Palmer BM. Differential metal content and
gene expression in rat left ventricular hypertrophy due to
hypertension and hyperactivity. J Trace Elem Med Biol.
2014 Jul;28(3):311-6.
Swenson AM, Trivedi DV, Rauscher AA, Wang Y,
Takagi Y, Palmer BM, Málnási-Csizmadia A, Debold EP,
Yengo CM. Magnesium modulates actin binding and
ADP release in myosin motors. J Biol Chem. 2014 Aug
22;289(34):23977-91.
Tanner BCW, McKnabb M, Palmer BM, Toth MJ, Miller
MS. Random myosin loss along thick-filaments increases
myosin attachment time and the proportion of bound
myosin heads to mitigate force decline in skeletal muscle.
Arch Biochem Biophys 552-553: 117-127, 2014.
Tanner BC, Wang Y, Robbins J, Palmer BM. Kinetics
of cardiac myosin isoforms in mouse myocardium are
affected differently by presence of myosin binding
protein-C. J Muscle Res Cell Motil. 2014 Dec;35(56):267-78.
Thompson NC, Stinnett-Donnelly J, Habel N, Benson
B, Bates JHT, Sobel BE, Spector PS. Improved spatial
resolution and electrogram wave direction independence
with the use of an orthogonal electrode Configuration. J
Clin Monit Comput (2014) 28:157-163.
Mun JY, Previs MJ, Yu HY, Gulick J, Tobacman LS, Beck
Previs S, Robbins J, Warshaw DM, Craig R. Myosinbinding protein C displaces tropomyosin to activate
cardiac thin filaments and governs their speed by an
independent mechanism. Proc Natl Acad Sci U S A. 2014
Feb 11;111(6):2170-5.
Wang Y, Bishop NM, Taatjes DJ, Narisawa S, Millán
JL, Palmer BM. Sex-dependent, zinc-induced
dephosphorylation of phospholamban by tissuenonspecific alkaline phosphatase in the cardiac
sarcomere. Am J Physiol Heart Circ Physiol. 2014 Sep
15;307(6):H933-8.
Previs MJ, Michalek AJ, Warshaw DM. Molecular
modulation of actomyosin function by cardiac myosinbinding protein C. Pflugers Arch. 2014 Mar;466(3):
439-44.
Zakeri R, Borlaug BA, McNulty SE, Mohammed SF,
Lewis GD, Semigran MJ, Deswal A, LeWinter M,
Hernandez AF, Braunwald E, Redfield MM. Impact of
atrial fibrillation on exercise capacity in heart failure with
preserved ejection fraction: a RELAX trial ancillary study.
Circ Heart Fail. 2014;7:123-30.
car diovascu l ar r e search i nstitute of ve r mont
•
2 0 14 a n n u a l r e p o r t
Hemostasis/Thrombosis
Ageno W, Di Minno MND, Ay C, Jang MJ,
Hansen JB, Steffen LM, Vaya M, Rattazzi M,
Pabinger I, Oh D, Di Minno G, Braekken AK,
Cushman M, Bonet E, Pauletto P, Squizzato A,
Dentali F. Association between the metabolic
syndrome, its individual components, and
unprovoked venous thromboembolism: results of
a patient-level meta-analysis. Arterioscler, Thromb
Vasc Biol 2014;34:2478-85.
Aleshnick M, Orfeo T, Brummel-Ziedins K, Gissel
M, Mann K. Interchangeability of rotational
elastographic instruments and reagents. J Trauma
Acute Care Surg. 2014;76:107-13.
Alexander KS, Zakai NA, Gillett S, McLure
LA, Wadley V, Unverzagt F, Cushman M. ABO
blood type, factor VIII and incident cognitive
impairment in the REGARDS cohort. Neurology
2014;30:1271-6.
Belalcazar LM, Anderson AM, Lang W, Schwenke
DC, Haffner SM, Yatsuya H, Rushing J, Vitolins
MZ, Reeves R, Pi-Sunyer FX, Tracy RP, Ballantyne
CM, Look ARG. Fiber intake and plasminogen
activator inhibitor-1 in type 2 diabetes: Look
ahead (action for health in diabetes) trial findings
at baseline and year 1. JAcad Nut Dietetics.
2014;114:1800-1810 e1802.
Bouchard BA, Gissel MT, Whelihan MF, Mann
KG, Butenas S. Platelets do not express the oxidized
or reduced forms of tissue factor. Biochim Biophys
Acta. 2014;1840:1188-93
Brummel-Ziedins K.E. Developing individualized
coagulation profiling of disease risk: thrombin
generation dynamic models of the pro and
anticoagulant balance Thromb.Research 2014; 133
Suppl 1:S9-S11.
Brummel-Ziedins K.E., Everse SJ, Mann KG,
Orfeo T. Modeling thrombin generation:
plasma composition based approach. J Thromb
Thrombolysis. 2014; 37(1):32-44.
Brummel-Ziedins K.E. and Wolberg A.S. Global
assays of hemostasis. Curr Opin Hematology 2014
21(5):395-403.
Cushman M. Thrombophilia testing in women
with venous thrombosis: the 4Ps approach. Clin
Chem 2014;60:134-7.
Cushman M, Callas PW, Allison MA, Criqui MH.
Inflammation and peripheral venous disease: the
San Diego Population Study. Thromb Haemost
2014; 112;566-72.
Dauerman HL. Reconsidering the necessity of
aspirin in stable coronary artery disease. J Am Coll
Cardiol. 2014; 64:1437-40.
Engbers MJ, Blom JW, Cushman M, Rosendaal
FR, van Hylckama Vlieg A. The contribution of
immobility risk factors to the incidence of venous
thrombosis in an older population. J Thromb
Haemost 2014;12:290-6.
Folsom AR, Lutsey PL, Nambi V, Defilippi
CR, Heckbert SR, Cushman M, Ballantyne
CM. Troponin T, NT-pro BNP, and venous
thromboembolism: The Longitudinal Investigation
of Thromboembolism Etiology (LITE). Vasc Med
2014;19:33-41.
Folsom AR, Lutsey PL, Roetker NS, Rosamond
WD, Lazo M, Heckbert SR, Basu S, Cushman M,
Selvin E. Elevated hepatic enzymes and incidence
of venous thromboembolism: a prospective study.
Ann Epidemiol 2014;24:817-21.e2.
Folsom AR, Roetker NS, Rosamond WD,
Heckbert SR, Basu S, Cushman M, Lutsey PL.
Serum 25-hydroxyvitamin D and risk of venous
thromboembolism: The Atherosclerosis Risk in
Communities (ARIC) Study. J Thromb Haemost
2014;12:1455-60.
Gebauer SK, Tracy RP, Baer DJ. Impact of stearic
acid and oleic acid on hemostatic factors in the
context of controlled diets consumed by healthy
men. Eur J Clin Nutr. 2014;68:1072-1074.
Hill AM, Stewart PW, Fung MK, Kris-Etherton
PM, Ginsberg HN, Tracy RP, Pearson TA, Lefevre
M, Reed RG, Elmer PJ, Holleran S, Ershow AG.
Monthly hemostatic factor variability in women
and men. Eur J Clin Invest. 2014; 44(3):309-318.
Holmes CE, Bambace NM, Lewis P, Callas PW,
Cushman M. Effectiveness of a short course of
complex lyM.P.H.edema therapy or compression
stocking therapy in the treatment of postthrombotic syndrome: a randomized controlled
trial. Vasc Med 2014;19:42-8.
Huang J, Huffman JE, Yamkauchi M, Trompet
S, Cushman M, Strachan DP, O’Donnell CJ.
Genome-wide association study for circulating
tissue plasminogen activator levels and functional
follow-up implicates endothelial STXBP5
and STX2. Arterioscler Thromb Vasc Biol
2014;34:1093-101.
Kahn SR, Comerata A, Cushman M, Evans,
NS, Ginsberg JS, Goldenberg NA, Prandoni
P, Vedantham S, Walsh ME, Weitz JI. The
posthrombotic syndrome: evidence-based
prevention, diagnosis and treatment strategies.
A Scientific Statement from the American
Heart Association Councils on Peripheral
Vascular Disease, Clinical Cardiology and
Cardiovascular and Stroke Nursing. Circulation
2014;130:1636-61.
Munir MS, Weng LC, Tang W, Basu S, Pankow
JS, Matijevic N, Cushman M, Boerwinkle E,
Folsom AR. Genetic markers associated with
plasma protein C level in African-Americans: the
Atherosclerosis Risk in Communities (ARIC)
study. Genet Epidemiol 2014;38:709-13.
Olson NC, Cushman M, Lutsey PL, McClure
LA, Judd S, Tracy RP, Folsom AR, Zakai NA.
Inflammation markers and incident venous
thromboembolism: the REasons for Geographic
and Racial Differences in Stroke (REGARDS)
cohort. J Thromb Haemost 2014 12:1993-2001.
Schneider DJ, Agarwal Z, Seecheran N, Keating
FK, Gogo P. Pharmacodynamic effects during the
transition between cangrelor and ticagrelor. JACC
Cardiovasc Int, 2014;7:435-42.
Schneider DJ, Seecheran N, Raza SS, Keating
FK, Gogo P. Pharmacodynamic effects during
the transition between cangrelor and prasugrel.
Coron Artery Dis 2015;26:42-8.
www . uvm . edu / medicine / cvri
19
Research Publications: A Sampling (continued)
Sharma D, Brummel-Ziedins KE, Bouchard B,
Holmes CE. Platelets in tumor progression: a
host factor with multiple potential targets in the
treatment of cancer. J Cellular Physiology 2014:
229:1005-15.
Zakai NA, Judd SE, Alexander K, McClure LA,
Kissela BM, Howard G, Cushman M. ABO blood
type and stroke risk: the Reasons for Geographic
Differences in Stroke (REGARDS) study. J Thromb
Haemost 2014;12:564-70.
Shea MK, Cushman M, Booth SL, Burke
GL, Chen H, Kritchevsky SB. Associations
between vitamin K status and hemostatic and
inflammatory biomarkers in community-dwelling
adults: the Multi-Ethnic Study of Atherosclerosis.
Thromb Haemost.2014; 112 .
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Steinhubl SR, Eikelboom JW, Hylek EM,
Dauerman HL, Smyth SS, Becker RC.
Antiplatelet therapy in prevention of cardioand venous thromboembolic events. Journal of
Thrombosis and Thrombolysis 2014; 37:367-372.
Undas A, Brummel-Ziedins KE, Mann KG
Anticoagulant effects of statins and their
clinical implications.. Thromb Haemost. 2014,
111:392-400.
Undas A, Brummel-Ziedins K, Mann KG.
Why does aspirin decrease the risk of venous
thromboembolism? On old and novel
antithrombotic effects of acetyl salicylic acid. J
Throm Haemost 2014, 12: 1776-87.
Agarwal I, Glazer NL, Barasch E, Biggs ML,
Djousse L, Fitzpatrick AL, Gottdiener JS, Ix JH,
Kizer JR, Rimm EB, Siscovick DS, Tracy RP,
Mukamal KJ. Fibrosis-related biomarkers and
incident cardiovascular disease in older adults:
The Cardiovascular Health Study. Circ Arrhythm
Electrophysiol. 2014; 7:583-9.
Agarwal I, Glazer NL, Barasch E, Biggs ML,
Djousse L, Fitzpatrick AL, Gottdiener JS, Ix
JH, Kizer JR, Rimm EB, Siscovick DS, Tracy
RP, Zieman SJ, Mukamal KJ. Fibrosis-related
biomarkers and risk of total and cause-specific
mortality: The Cardiovascular Health Study. Am J
Epidemiol. 2014; 179:1331-9.
Weng LC, Tang W, Rich SR, Smith NL, Redline
S, O’Donnell, CJ, Basu S Reiner AP, Delaney JA,
Tracy RP, Palmer CD, Young T, Yang Q, Folsom
AR, Cushman M. A genetic association study of
D-dimer with 50K SNPs from a candidate gene
chip in four ethnic groups. Thromb Res. 2014;
134: 462-7.
Allison MA, Jenny NS, McClellan RL,
Cushman M, Rifkin D. The associations
of adipokines with selected markers of the
renin-angiotensinogen-aldosterone system: the
Multi-Ethnic Study of Atherosclerosis. J Hum
Hypertens. 2014;29:127-33.
Whelihan MF, Kiankhooy A, Brummel-Ziedins
KE.Thrombin generation and fibrin clot
formation under hypothermic conditions: an in
vitro evaluation of tissue factor initiated whole
blood coagulation. J Crit Care. 2014;29:24-30.
Berkman A, Cole B, Ades PA, Dickey S, Higgins
ST, Trentham-Dietz A, Sprague BL, Lakoski SG.
Racial differences in breast cancer, cardiovascular
disease, and all-cause mortality among women
with ductal carcinoma in situ of the breast. Breast
Cancer Res Treat. 2014; 148:407-13.
Zakai NA, McClure LA, Judd SE, Safford MM,
Folsom AR, Lutsey PL, Cushman M. Racial and
regional differences in venous thromboembolism
in the United States in three cohorts. Circulation
2014;129:1502-9.
20
Ades PA. A Controversial Step Forward: A
Commentary on the 2013 ACC/AHA Guideline
on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults. Coron
Artery Dis. 2014 Feb 10.
Brown TM, Voeks JH, Bittner V, Brenner DA,
Cushman M, Goff DC, Glasser S, Muntner P,
Tabereaux PB, Safford MM. Achievement of
optimal medical therapy goals for US adults
with coronary artery disease: results from the
REasons for Geographic And Racial Differences
in Stroke (REGARDS) study. J Am Coll Cardiol
2014;63:1626-33.
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2 0 14 a n n u a l r e p o r t
Camacho A, Larsen B, McClelland RL, Morgan
C, Criqui M, Cushman M, Allison MA.
Association of subsyndromal and depressive
symptoms with inflammatory markers among
different ethnic groups: the Multi-Ethnic
Study of Atherosclerosis. J Affect Disord 2014;
164:165-70.
Cushman M, Judd SE, Howard VJ, Kissela
B, Gutiérrez OM, Jenny NS, Ahmed A,
Thacker EL, Zakai NA. N-terminal pro-B-type
natriuretic peptide and stroke risk: the Reasons
for Geographic and Racial Differences in Stroke
cohort. Stroke 2014;45:1646-50.
Ellis J, Lange EM, Li J, Dupuis J, Baumert J,
Walston JD, Keating BJ, Durda P, Fox ER, Palmer
CD, Meng YA, Young T, Farlow DN, Schnabel
RB, Marzi CS, Larkin E, Martin LW, Bis JC,
Auer P, Ramachandran VS, Gabriel SB, Willis
MS, Pankow JS, Papanicolaou GJ, Rotter JI,
Ballantyne CM, Gross M.D., Lettre G, Wilson JG,
Peters U, Koenig W, Tracy RP, Redline S, Reiner
AP, Benjamin EJ, Lange LA. Large Multiethnic
Candidate Gene Study for C-Reactive Protein
Levels: Identification of a Novel Association at
CD36 in African Americans. Hum Gen. 2014;
133: 985-95.
Fitzpatrick AL, Irizarry MC, Cushman M, Jenny
NS, Chi GC, Koro C. Lipoprotein-associated
phospholipase A2 and risk of dementia in the
Cardiovascular Health Study. Atherosclerosis
2014;235:384-91.
Gaalema DE, Higgins ST, Shepard DS, Suaya JA,
Savage PD, Ades PA. State-by-state variations in
cardiac rehabilitation participation are associated
with educational attainment, income, and
program availability. J Cardiopulm Rehabil Prev.
2014; 34:248-54.
Garg PK, Biggs ML, Carnethon M, Ix JH,
Criqui MH, Britton KA, Djousse L, SuttonTyrrell K, Newman AB, Cushman M, Mukumal
KJ. Metabolic syndrome and risk of incident
peripheral artery disease: the Cardiovascular
Health Study. Hypertension. 2014; 63:413-19.
Garin MC, Arnold AM, Lee JS, Tracy RP, Cappola AR.
Subclinical hypothyroidism, weight change, and body
composition in the elderly: The Cardiovascular Health
Study. J Clin Endocrinol Metab. 2014; 371:22-31.
Gillett SR, Boyle RH, Zakai NA, McClure LA,
Jenny NS, Cushman M. Validating laboratory results
in a national observational cohort study without
field centers: the Reasons for Geographic and
Racial Differences in Stroke Cohort. Clin Biochem
2014;47:243-6.
Holmes MV, Lange LA, Palmer T, Lanktree MB,
North KE, Almoguera B, Buxbaum S, Chandrupatla
HR, Elbers CC, Guo Y, Hoogeveen RC, Li J, Li YR,
Swerdlow DI, Cushman M, Price TS, Curtis SP, Fornage
M, Hakonarson H, Patel SR, Redline S, Siscovick DS,
Tsai MY, Wilson JG, van der Schouw YT, FitzGerald
GA, Hingorani AD, Casas JP, de Bakker PIW, Rich SS,
Schadt EE, Asselbergs FW, Reiner AP, Keating BJ. Causal
effects of body mass index on cardiometabolic traits and
events: a Mendelian randomization analysis. Am J Hum
Genet 2014;94:198-208.
Howard G, Wagenknecht LE, Kernan WN, Cushman
M, Thacker EL, Judd SE, Howard VJ, Kissela BM.
Racial differences in the association of insulin resistance
with stroke risk: the REasons for Geographic And
Racial Differences in Stroke (REGARDS) Study.
Stroke 2014;45:2257-62.
Karas MG, Benkeser D, Arnold AM, Bartz TM, Djousse
L, Mukamal KJ, Ix JH, Zieman SJ, Siscovick DS, Tracy
RP, Mantzoros CS, Gottdiener JS, Defilippi CR, Kizer
JR. Relations of plasma total and high-molecular-weight
adiponectin to new-onset heart failure in adults >/=65
years of age (from the cardiovascular health study). Am J
Cardiol. 2014; 113:328-34.
Kent ST, Cushman M, Howard G, Judd SE, Crosson
WL, Al-HaM.D.an MZ, McClure LA. Sunlight
exposure and cardiovascular risk factors in the
REGARDS study: a cross-sectional split-sample
analysis. BMC Neurol 2014;14:133.
Keteyian SJ, Squires R, Ades PA, Thomas R.
Incorporating patients with chronic heart failure
into outpatient cardiac rehabilitation: practical
recommendations for exercise and self-care counseling—
a clinical review. J Cardiopulm Rehabil Prev. 2014;
34:223-32.
Khawaja O, Maziarz M, Biggs ML, Longstreth WT, Jr.,
Ix JH, Kizer JR, Zieman S, Tracy RP, Mozaffarian D,
Mukamal KJ, Siscovick DS, Djousse L. Plasma free fatty
acids and risk of stroke in the Cardiovascular Health
Study. Int J Stroke. 2014; 9:917-20.
Kiage JN, Merrill PD, Judd SE, He K, Lipworth L,
Cushman M, Howard VJ, Kabagambe EK. Transfat intake and incidence of stroke in the REasons
for Geographic and Racial Differences in Stroke
(REGARDS) Cohort. Am J Clin Nutr. 2014; 99: 1071-6.
Kizer JR, Benkeser D, Arnold AM, Ix JH, Mukamal KJ,
Djousse L, Tracy RP, Siscovick DS, Psaty BM, Zieman
SJ. Advanced glycation/glycoxidation endproduct
carboxymethyl-lysine and incidence of coronary heart
disease and stroke in older adults. Atherosclerosis. 2014;
235:116-21.
Kraja AT, Chasman DI, North KE, Reiner AP, Yanek
LR, Kilpelainen TO, Smith JA, Dehghan A, Dupuis
J, Johnson AD, Feitosa MF, Tekola-Ayele F, Chu AY,
Nolte IM, Dastani Z, Morris A, Pendergrass SA, Sun
YV, Ritchie M.D., Vaez A, Lin H, Ligthart S, Marullo
L, Rohde R, Shao Y, Ziegler MA, Im HK, Cross
Consortia Pleiotropy Group, Cohorts for Heart and
Aging Research in Genetic Epidemiology, Genetic
Investigation of Anthropometric Traits Consortium,
Global Lipids Genetics Consortium, Meta-Analyses
of Glucose, Insulin-related Traits Consortium, Global
PBgen Consortium, ADIPOGen Consortium, Women’s
Genome Health Study, Howard University Family
Study, Schnabel RB, Jorgensen T, Jorgensen ME,
Hansen T, Pedersen O, Stolk RP, Snieder H, Hofman
A, Uitterlinden AG, Franco OH, Ikram MA, Richards
JB, Rotimi C, Wilson JG, Lange L, Ganesh SK, Nalls
M, Rasmussen-Torvik LJ, Pankow JS, Coresh J, Tang W,
Linda Kao WH, Boerwinkle E, Morrison AC, Ridker
PM, Becker DM, Rotter JI, Kardia SL, Loos RJ, Larson
MG, Hsu YH, Province MA, Tracy R, Voight BF,
Vaidya D, O’Donnell CJ, Benjamin EJ, Alizadeh BZ,
Prokopenko I, Meigs JB, Borecki IB. Pleiotropic genes
for metabolic syndrome and inflammation. Mol Genet
Metab. 2014; 112:317-38.
Lakoski SG, Mallick H, McClure LA, Safford M, Kissela
B, Howard G, Cushman M. A risk algorithm for assessing
short-term mortality for obese black and white men
and women: the REasons for Geographic and Racial
Differences in Stroke (REGARDS) cohort. Obesity
(Sliver Spring) 2014; 22:1142-8.
LeWinter C, Doherty P, Gale CP, Crouch S, Stirk L,
Lewin RJ, LeWinter ML Ades PA, Køber L, Bland MM.
Exercise-based cardiac rehabilitation in patients with heart
failure: a meta-analysis of randomized controlled trials
between 1999 and 2013. Eur J Prev Cardiol. 2014; Epub
ahead of print.
Logsdon BA, Dai JY, Auer PL, Johnsen JM, Ganesh
SK, Smith NL, Wilson JG, Tracy RP, Lange LA, Jiao S,
Rich SS, Lettre G, Carlson CS, Jackson RD, O’Donnell
CJ, Wurfel MM, Nickerson DA, Tang H, Reiner AP,
Kooperberg C. A variational bayes discrete mixture test
for rare variant association. Genet Epidemiol. 2014;
38:21-30.
Matteini AM, Li J, Lange EM, Tanaka T, Lange LA,
Tracy RP, Wang Y, Biggs ML, Arking DE, Fallin M.D.,
Chakravarti A, Psaty BM, Bandinelli S, Ferrucci L,
Reiner AP, Walston JD. Novel gene variants predict
serum levels of the cytokines IL-18 and IL-1Ra in older
adults. Cytok 2014; 65:10-6.
McClure LA, Kleindorfer DO, Kissela BM, Cushman
M, Soliman EZ, Howard G. Assessing the performance
of the Framingham Stroke Risk Score in the Reasons
for Geographic and Racial Differences in Stroke cohort.
Stroke 2014;45:1716-20.
Miedema M.D., Maziarz M, Biggs ML, Zieman SJ,
Kizer JR, Ix JH, Mozaffarian D, Tracy RP, Psaty BM,
Siscovick DS, Mukamal KJ, Djousse L. Plasma-free
fatty acids, fatty acid-binding protein 4, and mortality
in older adults (from the Cardiovascular Health Study).
Am J Cardiol. 2014; 114:843-8.
Muntner P, Colantonio L, Cushman M, Goff DC,
Howard G, Howard VJ, Kissela B, Levitan EM, LloydJones DM, Safford MM. Validation of the Atherosclerotic
Cardiovascular Disease Pooled Cohort Risk Equations.
JAMA 2014;311:1406-15.
Muntner P, Safford MM, Cushman M, Howard
G. Comment on the reports of over-estimation of
ASCVD risk using the 2013 AHA/ACC risk equation.
Circulation 2014;129:266-7.
Muse ED, Feldman DI, Blaha MJ, Dardari ZA,
Blumenthal RS, Budoff MJ, Nasir K, Criqui MH,
Cushman M, McClelland RL, Allison MA. The
association of resistin with cardiovascular disease in the
Multi-Ethnic Study of Atherosclerosis. Atherosclerosis.
2014; 239:101-8.
www . uvm . edu / medicine / cvri
21
Research Publications: A Sampling (continued)
Myocardial Infarction Genetics Consortium I.
Inactivating mutations in npc1l1 and protection from
coronary heart disease. NEJM. 2014; 371:2072-82.
NHLBI Grand Opportunity Exome Sequencing
Project. Whole-exome sequencing identifies rare and
low-frequency coding variants associated with LDL
cholesterol. Am J Hum Genet. 2014; 94:233-45.
Odden MC, Shlipak MG, Whitson H, Katz R, Kearney
PM, Defilippi C, Shastri S, Sarnak MJ, Siscovick DS,
Cushman M, Psaty BM, Newman AB. Risk factors
for cardiovascular disease across the spectrum of older
age: the Cardiovascular Health Study. Atherosclerosis
2014;237:336-42.
Ong KL, McClelland RL, Rye K, Cheung BMY,
Post WS, Vaidya D, Criqui MH, Cushman M, Barter
PJ, Allison MA. The relationship between insulin
resistance and vascular calcification in coronary
arteries, and the thoracic and abdominal aorta: The
Multi-Ethnic Study of Atherosclerosis. Atherosclerosis
2014;236:257-62.
Pack QR, Rodriguez-Escudero JP, Thomas RJ, Ades PA,
West CP, Somers VK, Lopez-Jimenez F. The prognostic
importance of weight loss in coronary artery disease: a
systematic review and meta-analysis. Mayo Clin Proc.
2014; 89:1368-77.
Rengo JL, Savage PD, Toth MJ, Ades PA. Statin therapy
does not attenuate exercise training response in cardiac
rehabilitation. J Am Coll Cardiol. 2014; 63:2050-1.
Sanders JL, Ding V, Arnold AM, Kaplan RC, Cappola
AR, Kizer JR, Boudreau RM, Cushman M, Newman
AB. Do changes in circulating biomarkers track with each
other and with functional changes in older adults? J Am
Geriatr Soc. 2014; 69:174-81.
Soliman EZ, Safford MM, Muntner P, Khodneva Y,
Dawood FZ, Zakai NA, Thacker EL, Howard VJ,
Howard G, Herrington DH, Cushman M. Atrial
fibrillation and the risk of myocardial infarction. JAMA
Intern Med 2014;174:107-14.
Suzuki T, Voeks J, Zakai NA, Jenny NS, Brown TM,
Safford MM, LeWinter M, Howard G, Cushman M.
Metabolic syndrome, C-reactive protein and mortality
in U.S. blacks and whites: the REasons for Geographic
and Racial Differences in Stroke (REGARDS) study.
Diabetes Care. 2014; 37: 2284-90.
22
Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes
MV, Engmann JE, Shah T, Cushman M, … Keating BJ,
Hingorani AD, Sattar N. HMG-coenzyme A reductase
inhibition, type 2 diabetes and bodyweight: evidence
from genetic analysis and randomized trials. Lancet
2014;385:351-61.
Zemaitis P, Durazo R, Liu K, Jacobs D, Cushman
M, Cooper R, Kramer H. Cumulative systolic blood
pressure and changes in urine albumin/creatinine
ratios in non-diabetic participants of the Multi-Ethnic
Study of Atherosclerosis. Can J Am Soc Nephrol
2014;9:1922-9.
Thacker EL, Gillett SR, Wadley VG, Unverzagt FW,
Judd SE, McClure LA, Howard VJ, Cushman M. The
American Heart Association’s Life’s Simple 7 and incident
cognitive impairment: the Reasons for Geographic and
Racial Differences in Stroke (REGARDS) study. J Am
Heart Assoc 2014;3:e000635.
Vascular Biology/Vascular Intervention/
Myocardial Infarction/Stroke
Triglyceride and Hdl Working Group of the Exome
Sequencing Project NHLBI. Loss-of-function
mutations in apoc3, triglycerides, and coronary disease.
N Engl J Med. 2014;371:22-31.
Waterworth DM, Li L, Scott R, Warren L, Gillson C,
Aponte J, Sarov-Blat L, Sprecher D, Dupuis J, Reiner
A, Psaty BM, Tracy RP, Lin H, McPherson R, Chissoe
S, Wareham N, Ehm MG. A low-frequency variant in
mapk14 provides mechanistic evidence of a link with
myeloperoxidase: A prognostic cardiovascular risk
marker. J Am Heart Assoc. 2014; 3: e001074.
Weiner SD, Ahmed HN, Jin Z, Cushman M, Herrington
DH, Nelson JC, Di Tullio MR, Homma S. Systemic
inflammation and brachial artery endothelial function
in the Multi-Ethnic Study of Atherosclerosis. Heart
2014;100:862-6.
Whitson HE, Arnold AM, Yee LM, Mukamal KJ,
Kizer JR, Djousse L, Ix JH, Siscovick D, Tracy RP,
Thielke SM, Hirsch C, Newman AB, Zieman S. Serum
carboxymethyl-lysine, disability, and frailty in older
persons: The Cardiovascular Health Study. J Gerontol
A Biol Sci Med Sci. 2014; 69:710-6.
Womack JA, Chang CC, So-Armah KA, Alcorn C,
Baker JV, Brown ST, Budoff M, Butt AA, Gibert C,
Goetz MB, Gottdiener J, Gottlieb S, Justice AC, Leaf
D, McGinnis K, Rimland D, Rodriguez-Barradas MC,
Sico J, Skanderson M, Tindle H, Tracy RP, Warner A,
Freiberg MS. HIV infection and cardiovascular disease
in women. J Am Heart Assoc. 2014; 3:e001035.
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Ackerman S, Watkins MW, Kostial AF, Rabinowitz T.
Urgent Assessment of Decision-Making Capacity in a
Patient With Schizophrenia and an Evolving Myocardial
Infarction Who is Refusing Care. J. Psychosomatics. 2014
Dec 12.
Cipolla MJ, Chan SL, Sweet JG, Tavares MJ, Gokina
N, Brayden JE. Postischemic reperfusion causes smooth
muscle calcium sensitization and vasoconstriction of
parenchymal arterioles. Stroke. 2014; 45:2425-30.
Cipolla MJ, Sweet J, Chan SL, Tavares MJ, Gokina
N, Brayden JE. Increased pressure-induced tone in rat
parenchymal arterioles vs. middle cerebral arteries: role of
ion channels and calcium sensitivity. J Appl Physiol, 2014;
117:53-9.
Dauerman HL. Death and interventional cardiology: a
tale of 2 trials. Circulation. 2014;130:1442-4.
Dauerman HL. Deconstructing the language of bleeding.
J Am Coll Cardiol. 2014; 63:1876-8.
Dunn KM, Nelson MT. Neurovascular signaling in the
brain and the pathological consequences of hypertension.
Am J Physiol Heart Circ Physiol. 2014;306:H1-14.
Gonzales AL, Yang Y, Sullivan MN, Sanders L,
Dabertrand F, Hill-Eubanks DC, Nelson MT, Earley S. A
PLCγ1-dependent, force-sensitive signaling network in
the myogenic constriction of cerebral arteries. Sci Signal.
2014; 7:ra49.
Hill-Eubanks DC, Gonzales AL, Sonkusare SK, Nelson
MT. Vascular TRP channels: performing under pressure
and going with the flow. Physiology (Bethesda). 2014;
29:343-60.
Koide M, Syed AU, Braas KM, May V, Wellman GC
(2014). Pituitary adenylate cyclase activating polypeptide
(PACAP) dilates cerebellar arteries through activation
of large-conductance Ca(2+)-activated (BK) and ATPsensitive (K ATP) K (+) channels. J Mol Neurosci. 2014
Nov;54:443-50.
2 0 14 a n n u a l r e p o r t
Krishnamoorthy G, Sonkusare SK, Heppner TJ,
Nelson MT. Opposing roles of smooth muscle BK
channels and ryanodine receptors in the regulation
of nerve-evoked constriction of mesenteric
resistance arteries. Am J Physiol Heart Circ Physiol.
2014; 306:H981-8.
Li Y, Baylie RL, Tavares MJ, Brayden JE (2014).
TRPM4 channels couple purinergic receptor
mechanoactivation and myogenic tone development
in cerebral parenchymal arterioles. J Cereb Blood
Flow Metab. 2014 Oct;34(10):1706-14.
Longden TA, Dabertrand F, Hill-Eubanks DC,
Hammack SE, Nelson MT. Stress-induced
glucocorticoid signaling remodels neurovascular
coupling through impairment of cerebrovascular
inwardly rectifying K+ channel function. Proc Natl
Acad Sci USA. 2014; 111:7462-7.
Longden TA, Hammack SE, Nelson MT.
Channeling Stress: inwardly-rectifying K+ channels
in stress and disease. Channels (Austin). 2014;
8:296-7.
Mercado J, Baylie R, Navedo MF, Yuan C, Scott
JD, Nelson MT, Brayden JE, Santana LF. Nanoscale
signaling between AKAP150, PKC, and TRPV4
channels in arterial smooth muscle. J Gen Physiol
2014; 143(5): 559-575.
Mingin GC, Peterson A, Erickson CS, Nelson
MT, Vizzard MA. Social stress induces changes in
urinary bladder function, bladder NGF content
and generalized bladder inflammation in mice.
Am J Physiol Regul Integr Comp Physiol. 2014;
307:R893-900.
Nausch B, Rode F, Jorgensen S, Nardi A, Korsgaard
MP, Hougaard C, Brown WD, Bonev AD, Dyhring
T, Strobaek D, Olesen SP, Christophersen P, Grunnet
M, Nelson MT, Ronn LC. NS19504: a novel BK
channel activator with relaxing effect on bladder
smooth muscle spontaneous phasic contractions. J
Pharmacol Exp Ther. 2014; 350:520-30.
Sonkusare SK, Dalsgaard T, Bonev AD, HillEubanks DC, Kotlikoff MI, Scott JD, Santana LF,
Nelson MT. AKAP150-dependent cooperative
TRPV4 channel gating is central to endotheliumdependent vasodilation and is disrupted in
hypertension. Sci Signal. 2014; 7:ra66.
Taylor KA, Feig M, Brooks CL 3rd, Fagnant PM,
Lowey S, Trybus KM. Role of the essential light
chain in the activation of smooth muscle myosin
by regulatory light chain phosphorylation. J Struct
Biol. 2014 Mar;185(3):375-82.
Johnson A, Chan S-L, Tremble S, Moseley J,
LaMarca B, Nagle K, Cipolla MJ. Magnesium
sulfate treatment reverses seizure susceptibility and
decreases neuroinflammation in a rat model of severe
preeclampsia. PLoS One. 2014; 9:e113670.
Tian J, Dauerman H, Toma C, Samady H, Itoh
T, Kuramitsu S, Domei T, Jia H, Vergallo R,
Soeda T, Hu S, Minami Y, Lee H, Yu B, Jang IK.
Prevalence and characteristics of TCFA and degree
of coronary artery stenosis: an OCT, IVUS, and
angiographic study. J Am Coll Cardiol. 2014;
64:672-80.
Johnson A, Chan S-L, Tremble S, Moseley
J, LaMarca B, Nagle K, Cipolla MJ (2014):
Magnesium sulfate treatment reverses seizure
susceptibility and decreases neuroinflammation in
a rat model of severe preeclampsia. PLOS ONE
9(11):e113670.
Tian J, Ren X, Uemura S, Dauerman H, Prasad
A, Toma C, Jia H, Abtahian F, Vergallo R, Hu
S, McNulty I, Lee H, Lee S, Yu B, Jang IK.
Spatial heterogeneity of neoatherosclerosis and
its relationship with neovascularization and
adjacent plaque characteristics: optical coherence
tomography study. Am Heart J. 2014; 167:884-92.
van Diepen S, Reynolds HR, Stebbins A, Lopes
RD, Džavík V, Ruzyllo W, Geppert A, Widimsky
P, Ohman EM, Parrillo JE, Dauerman HL, Baran
DA, Hochman JS, Alexander JH. Incidence
and outcomes associated with early heart failure
pharmacotherapy in patients with ongoing
cardiogenic shock. Crit Care Med. 2014;42:
281-288.
Villalba N, Sonkusare SK, Longden TA, Tran
TL, Sackheim AM, Nelson MT, Wellman GC,
Freeman K. Traumatic brain injury disrupts
cerebrovascular tone through endothelial
inducible nitric oxide synthase expression and
nitric oxide gain of function, J Am Heart Assoc.
2014; 3:e001474.
Vascular Function in Pregnancy:
Preeclampsia
Bernstein IM. The relationship of a family history
for hypertension, myocardial infarction, or stroke
with cardiovascular physiology in young women.
Reprod Sci. 2014; 21:509-16.
Buhimschi IA, Nayeri UA, Zhao G, Shook LL,
Pensalfini A, Funai EF, Bernstein IM, Glabe CG,
Buhimschi CS. Protein misfolding, congophilia,
oligomerization, and defective amyloid processing
in preeclampsia. Sci Transl Med. 2014; 6:245ra91.
Mann SE, Maille N, Clas D, Osol G. Perivascular
adipose tissue: a novel regulator of vascular
tone in the rat pregnancy. Reprod Sci. 2014;
pii:1933719114561556.
McBride C, Hale SA, Subramanian M, Badger GJ,
Schreurs M.P.H. and Cipolla MJ. Cerebrovascular
dysfunction and blood-brain barrier permeability
induced by oxidized LDL are prevented by apocynin
and magnesium sulfate. J Cardiovasc Pharm. 2014;
63:33-9.
Merhi Z, Doswell A and Cipolla MJ (2014):
Vitamin D alters genes involved in follicular
development and steroidogenesis in human cumulus
granulosa cells. J Clin Endo & Metab 63(1):33-9.
Osol G, Bernstein I. Preeclampsia and maternal
cardiovascular disease: consequence or
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Osol G, Moore LG. Maternal uterine vascular
remodeling during pregnancy. Microcirculation.
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Sammar M, Nisamblatt S, Gonen R, Huppertz
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www . uvm . edu / medicine / cvri
23
In Memory of
Burton E. Sobel, M.D.
University Distinguished Professor of Medicine
E.L. Amidon Professor and Chair of Medicine
Founding Director, Cardiovascular Research Institute of Vermont
An inspiring and internationally-recognized leader in cardiovascular medicine, Dr. Sobel
founded the Cardiovascular Research Institute of Vermont (CVRI) in 2002 and served
as its Director until his death in 2013. To honor his memory and continue his legacy, the
Burton E. Sobel, M.D. Memorial Fund was established at the University of Vermont.
A
fter graduating from Cornell
University, Dr. Sobel obtained his
M.D. from Harvard Medical School
(magna cum laude) followed by a
residency in Internal Medicine at Peter
Bent Brigham Hospital and cardiology
training at the National Institutes of
Health. He began his career on the
faculty at the University of California
San Diego and then joined Washington
University in St. Louis as Director of
the Cardiovascular Disease Division.
He subsequently rose to become
Distinguished Professor in Cardiovascular
Disease and Director of the Center
for Cardiovascular Research. In 1994,
Dr. Sobel relocated to the University
of Vermont to lead the Department
of Medicine, and was honored as an
inaugural University Distinguished
Professor in 2009.
24
He received many prestigious awards;
led diverse research and training programs
funded by the National Institutes
of Health, the American Diabetes
Association, and the American Heart
Association; published more than 800
manuscripts; edited major cardiovascular
and medical scientific journals; and held
several patents.
Dr. Sobel was a consummate scholar.
Research he led was responsible for
enzymatic sizing of myocardial infarction
and subsequently thrombolytic therapy
for the treatment of ST elevation
myocardial infarction. During the past
two decades Dr. Sobel focused his energy
on diabetes and particularly the role of
plasminogen activator inhibitor type-1
(PAI-1). During his career he was the
editor or associate editor of top medical
journals including Circulation, the
car diovascu l ar r e search i nstitute of ve r mont
•
Journal of Clinical Investigation, American
Journal of Physiology and Coronary Artery
Disease and served on numerous scientific
advisory committees for the NIH and
other premier research organizations.
He was also a highly regarded leader
in subspecialty societies including the
American College of Cardiology, the
American Heart Association and the
Society for Experimental Biology and
Medicine. Dr. Sobel’s contributions
were nationally recognized through
numerous honors and awards including
Distinguished Scientist of the American
College of Cardiology, election to the
Society of Clinical Investigation, and the
2010 Distinguished Scientist Award from
the Society for Experimental Biology and
Medicine, who also honored him with the
named Burton E. Sobel Annual Young
Investigator Award.
2 0 14 a n n u a l r e p o r t
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