Vyacheslav A. Korshunov, Ph.D.

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Research

•My research interests are focused on the underlying genetic mechanisms of vascular remodeling and its impact on the progression and treatment of cardiovascular diseases

Research Overview

Every year millions of individuals are diagnosed having coronary disease, and approximately a million myocardial infarctions and 500,000 coronary deaths reported per year in the United States alone. A critical role for low endothelial shear stress and plaque burden (clinically defined as intima-media thickening (IMT)) was found in a number of clinical trials. But mechanism by which vessel remodel remains unclear. We have developed a flow-dependent model of vascular remodeling in a mouse. In fact, this animal model significantly reproduced characteristics of human diseased arteries also called a "Glagov's phenomenon".

Both animal experiments and human epidemiological studies suggest a significant genetic factor in vascular remodeling. Our recent observations in low flow-induced vascular remodeling in 5 inbred mouse strains emphasized the role of genetic factors in the ability of blood vessels to obey "Glagov's phenomenon". First, according to "Glagov's phenomenon" there was a significant correlation between increased IMT (thickness) and increased carotid size to maintain lumen diameter constant and therefore flow constant. However, there were also significant strain-dependent differences in the remodeling index (measured as the slope of size/thickness). For example, FVB mice increased size twice as much as SJL mice for the same increase in thickness. The difference in remodeling index among these mouse strains proves that vascular remodeling has strong genetic influences and suggests that fundamental alterations in sensing changes in blood flow and/or transducing hemodynamic signals contribute to these genetic differences.

To appreciate complexity of remodeling process we also used a single gene approach to demonstrate that a receptor tyrosine kinase, Axl (Ark, Ufo, Tyro7) play a significant role in vascular remodeling. In particular, we have found that Axl is an important signaling mediator for oxidative stress in cultured vascular smooth muscle cells and intact vessels. Intimal proliferation and medial growth were significantly decreased in a cuff injury model in Axl knockout mice compared with wild-type Axl knockout mice. Recently we demonstrated an important role for Gas6/Axl pathway in flow-dependent remodeling by regulating not only apoptosis of carotid IMT but also vascular inflammation. We are also working towards a new concept for anti-hypertensive treatment by studying the role for anti-apoptotic Gas6/Axl pathway.

Current Appointments

• Assistant Professor - Department of Medicine, Aab Cardiovascular Research Institute (SMD)

Lab Description

Flow-dependent model of vascular remodeling in mouse. Animal model significantly reproduced characteristics of human diseased arteries also called a "Glagov's phenomenon".

Lab Website

http://www.urmc.rochester.edu/cvri/research/berk-lab.cfm