Spring 2007 Newsletter

Coronary Arterial Dynamics and Atherogenesis

Scott VanEpps, Ruth L. Kirschstein Predoctoral Fellow in David Vorp’s lab and associate professor of bioengineering and surgery, is completing his NIH-funded F31 research grant on Coronary Arterial Dynamics and Atherogenesis.

Although risk factors for atherosclerosis (AS) are systemic in nature, certain arteries (e.g., coronary arteries) are more susceptible to AS than others. The highly susceptible coronary arteries experience the added mechanical forces of cyclic flexing, stretching, and twisting due to their tethering to a beating heart suggesting that both shear and mural stress are contributors to AS.

Fellowship Goals

VanEpps’ hypothesis is that local variations in shear and mural stress associated with dynamic motion of arterial segments influence the distribution of early markers of atherogenesis. His goals with this fellowship are to (1) determine experimentally the extent and spatial distribution of early markers (i.e., endothelial injury, lipid accumulation, and inflammatory activation) of atherogenesis in intact arterial segments exposed to physiologically realistic ex vivoperfusion conditions including cyclic flexure, stretch, and twist; (2) estimate the shear and mural stress distributions specifically for each experimentally perfused arterial segment using computational fluid dynamics and computational solid stress analyses, respectively; and (3) determine the correlative relationships between the shear and mural stress distributions estimated computationally and the spatial variation of atherogenic endpoints determined experimentally.

The problem being addressed

In layman’s terms, the major problem being addressed by VanEpps’ study is the prevention of heart attacks that can result from blockages in the blood vessels that supply oxygen and other nutrients to the heart. In order to prevent these plaques and the heart attacks that can result from them, it is imperative to understand what makes these vessels different from other arteries and thus more susceptible. One obvious difference is that these vessels are physically attached to the heart and, therefore, are deformed by the contraction of the beating heart muscle, causing the vessels to undergo complex deformations such as bending, stretching, and twisting. The goal of this particular study is to understand how these motions affect a vessel’s susceptibility to the formation of plaques.

Does bending, stretching, and twisting of a blood vessel change the expression of these genes and proteins?

Several genes and proteins associated with the formation of plaques have been identified. The question VanEpps is trying to answer in this study is: Does bending, stretching, and twisting of a blood vessel change the expression of these genes and proteins?  Vorp’s laboratory has devised a unique experimental system that allows researchers to keep “alive” vessels that have been surgically removed from an animal while exposing them to various motions, such as bending, stretching, and twisting. Biological tests can then be performed to determine the level of expression of the various genes and proteins. This system will allow VanEpps to compare vessels that are deformed by these motions to vessels that are not deformed.

The goal of the research is to understand why plaques form in certain vessels and not others. This will allow physicians to focus their prevention and treatment strategies toward the vasculature that is most susceptible. Furthermore, he hopes to find new risk factors that may aid in the prevention and/or early detection of heart disease.

About Scott

Scott VanEpps is currently completing both the MD and the PhD in bioengineering simultaneously (he is one of 10 MD/PhD in bioengineering candidates), while completing the research study for his F31 in Vorp’s lab. VanEpps graduated summa cum laude from Pitt in 2001 with bachelor’s degrees in chemical engineering and molecular biology.

VanEpps was in his first two years of medical school when he realized that he wanted to focus his research on the cardiovascular system. VanEpps says, “I was intrigued not only with the complexity of what is known about the heart and the vasculature, but also the amount of unknowns leading to disease. I committed myself to mastering these known complexities and pushing the frontiers of the unknown.”  He learned that Vorp’s Vascular Biomechanics Research Laboratory would be an ideal environment for him because the research in the lab applies engineering principles to the clinical problems of abdominal aortic aneurysm, atherosclerosis, and bypass graft failure. “Having interviewed with Vorp during my application period I remember being enthralled by the work that he was doing in his lab,” he says. “After a 10-week research rotation in his lab I knew that we would make an excellent mentor-student match.”

His ECMO role and work in the community

Like Timothy Maul, who also received an F31 grant, VanEpps works as an ECMO (extracorporeal membrane oxygenator) technician at Children’s Hospital. He is involved in many community outreach programs, such as serving as a volunteer assistant for the Carnegie Science Center Overnighter, where he assists in the explanation of molecular biology techniques used in crime solving and helps organize and run an assembly line for setting up polymerase chain reactions (PCR). He also participated in a mission to provide medical supplies and care to the impoverished people of Guatemala as a medical missionary for Global Development Services.

Read About another Outstanding Graduate Researcher

Graduate student Timothy Maul also received an F31 grant. Read “The Mechanical Stimulation of Bone Marrow Derived Progenitor Cells.”

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