Kumar examines SUMOs’ role in endothelial dysfunction

Santosh Kumar, PhD, associate in Cardiovascular Medicine, received a five-year, $2M grant from the NIH’s National Heart, Lung, and Blood Institute for his project “SUMO2-p66shc axis in vascular endothelial dysfunction and atherosclerosis.” With this R01, he will investigate the expression of the gene SUMO2 in the lining of arteries and veins, the correlation between SUMO2ylation and atherosclerosis, and the mechanism behind SUMO2lyation’s effect on oxidative stress in the arteries.

SUMOylation refers to the process of post-translational modification and union of small ubiquitin-like modifier proteins (SUMOs) to lysine residues. These lysine residues target proteins and affect their function, localization, or stability. Previous research suggests SUMOylation of SUMO2/3 impedes the function of the inner layer of cells lining the arteries and veins, also known as the endothelium. Furthermore, these studies also indicate that SUMOylation accelerates atherosclerosis, which occurs when fatty plaque builds up in the vascular endothelial of the arteries.

Kumar’s study will identify a novel target for SUMOylation in the vascular endothelium. Specifically, he will look at the p66Shc protein, a master redox regulator, and vascular oxidative stress and function.

“We have observed that SUMO2 overexpression in endothelial cells promotes oxidative stress and impairs endothelial function,” Kumar said. “Furthermore, we have observed that p66Shc is directly modified by SUMO2 on a critical lysine that regulates the oxidative property of p66Shc. Based on this evidence, we hypothesize that SUMO2ylation of p66Shc is a key molecular mechanism driving vascular oxidative stress, endothelial dysfunction, and atherosclerosis.”

Through this research, Kumar says the team will be able to advance the knowledge of SUMO2-directed therapies that could treat atherosclerotic vascular disease.




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