Looking at the Future of Cardiovascular Health through the Lens of Early-Career Investigators

February 22, 2023 by Jennifer Nachbur

The University of Vermont’s Larner College of Medicine features some of the world’s foremost cardiovascular researchers, experts in cardiovascular disease risk factors, thrombosis, atherosclerosis, stroke, and heart failure. the science shared by early-career investigators at the Cardiovascular Research Institute of Vermont’s fourth annual Viridis Montis Challenge, it was apparent that the institution’s reputation and legacy in the field of cardiovascular research will continue to have a global impact.

(L-R) Noma Anderson; David Schneider; Toishi Sharma; Amreen Mughal; Ryan Hunt; Aaron Lambert; Samuel Short; and Diann Gaalema (Photo: David Seaver)

Despite its rural location, the University of Vermont’s (UVM) Larner College of Medicine features some of the world’s foremost cardiovascular researchers. Many of the college’s clinical and basic science faculty are renowned experts and researchers in areas including cardiovascular disease risk factors, thrombosis, atherosclerosis, stroke, and heart failure. In addition, UVM is home to the Cardiovascular Research Institute of Vermont (CVRI), which promotes collaboration, cross-disciplinary research, and supports career development with an emphasis on early career investigators,

At the CVRI’s fourth annual Viridis Montis Early Career Investigator Challenge on February 1, it was apparent that the institution’s reputation and legacy in the field of cardiovascular research will continue to have a global impact.

The five finalists – UVM and UVM Medical Center early-career investigators from diverse cardiovascular research backgrounds – presented research on topics including cardiovascular risk in women, cerebral blood flow and stroke, endothelial function and coagulation, and preventing stroke and understanding its impact on cerebral arteries.

A marker for cardiovascular disease risk in women

"Cardiovascular death is the leading cause of death in women, both globally, as well as in the United States,” said Toishi Sharma, M.B.B.S., a cardiovascular disease fellow in the Department of Medicine conducting research under the mentorship of David Schneider, M.D., professor of medicine, medical director of cardiovascular services, and director of the CVRI. “For over three decades, the cardiovascular death rate has remained higher for women compared to men," said Sharma, who was the winner of the 2023  Viridis Montis competition.

Sharma noted that, regardless of these statistics, no predictive or prognostic tool to identify women at increased risk exists. In her presentation on “Platelet FcγRIIa expression, a powerful marker of cardiovascular risk in women,” Sharma explained that Fc gamma R2a (FcγRIIa) is found on the surface of platelets, amplifies platelet activation, and promotes the thrombosis (clotting) process. This research showed that women with a higher FcγRIIa levels had a higher risk for clotting and related clinical events such as stroke or heart attack.

Gaining a better understanding of the mechanisms impacting stroke disability

“Every 40 seconds, someone in the United States has a stroke, according to the American Heart Association,” said Ryan Hunt, one of the finalists selected to present research during the competition. A second-year Neuroscience Graduate Program student working in the laboratory of Marilyn Cipolla, Ph.D., professor of neurological sciences, he presented on “Human stroke serum causes endothelial dysfunction in healthy non-ischemic cerebral arteries.”

During his talk, Hunt described dynamic autoregulation, which is the ability of blood vessels to regulate the amount on blood flow to the brain under different conditions. Research has shown that this function is impaired in both ischemic (blood clot blockage of an artery in the brain) and hemorrhagic (ruptured blood vessel in the brain) stroke. To determine the potential role of the proteins released into the bloodstream following stroke in causing cerebrovascular disruption, Hunt and colleagues examined serum from patients who had experience different types of stroke – cardioembolic, small vessel disease, and intracerebral hemorrhage. Their findings suggest that circulating factors elevated after several different types of stroke are damaging to the blood vessels in the brain’s contralateral hemisphere. In addition, he was able to isolate the effect of circulating factors in serum on non-ischemic cerebral artery function.

The role of electrical and calcium signaling in cerebral brain flow

Amreen Mughal, Ph.D. Assistant Professor of Pharmacology (mentor: Mark Nelson, Ph.D., University Distinguished Professor and Chair of Pharmacology) "Electro-Calcium coupling in the brain endothelium: A higher order mechanism to control cerebral blood flow." Her research, which aims to better understand the relationship between electrical and calcium signaling and the mechanisms involved, featured a three-dimensional view of calcium signaling that allowed a glimpse into even the smallest events occurring during this process. "By knowing the mechanism in the physiological condition, we can extend the phenomena in the pathological condition, and that would allow us to identify what kind of interventions" can be developed for dementia and related conditions in the future,” said Mughal.

Investigating mechanisms impacting the coagulation process in traumatic injury

Aaron Lambert, M.D., a clinical instructor and third-year general surgery resident at UVM Medical Center, conducts research in the Trauma Physiology Laboratory led by Kalev Freeman, M.D., Ph.D., professor of emergency medicine. The lab’s work focuses on improving outcomes for trauma patients by increasing knowledge about the responses of small blood vessels to injury, since abnormal clotting or bleeding often occurs following a traumatic injury. His presentation titled “Endothelial-Specific Ablation of the TMEM16F Scramblase Reduces In Vivo Clot Formation in Mice" described a process that the research team tested in which the TMEM16F protein was isolated to examine the broader endothelial role in coagulation. After performing an endothelial specific ablation of the TMEM16F protein Lambert and his colleagues observed decreased thrombus formation and increased bleeding times.

Identifying alternative risk measurements for stroke in atrial fibrillation patients

Samuel Short, a Class of 2023 medical student mentored by Mary Cushman, M.D., M.Sc., professor and vice chair for emerging researchers in the Department of Medicine, presented on "Multiple blood biomarkers improve stroke risk prediction in a large cohort with atrial fibrillation."

Atrial fibrillation (AF) – the most common type of heart arrhythmia – is associated with a higher stroke risk and requires treatment with anti-coagulation therapies. To determine the level of stroke risk and treatment, clinicians typically use the CHA₂DS₂-VASc tool – a scoring system that considers nine different risk factors, including hypertension, type 2 diabetes, and age above 75 years old. "Blood biomarkers of stroke risk are thought to be key additional pieces of information" to determining stroke risk for AF patients, said Short, who used data from the longitudinal REGARDS study to find out if there were ways to improve the standard risk stratification process. He and colleagues studied the more than 2000 REGARDS participants with AF, measuring nine different blood markers known for stroke risk in the REGARDS participants’ blood samples. They discovered that risk prediction was substantially improved when two biomarkers -- NTproBNP and GDF-15 – were added to the risk assessment, in comparison to using the CHA₂DS₂-VASc scoring tool alone.

Like their UVM mentors, the goal of these early-career investigators is to increase understanding of the causes and consequences of cardiovascular disease and reduce the incidence, disability, and death caused by heart and vascular diseases through improving prevention, diagnosis, and treatment.

Learn more about the Cardiovascular Research Institute.