Christopher Pattillo, PhD, Associate Professor of Molecular and Cellular Physiology, has received a $1,825,000 R01 grant from the National Heart, Lung, and Blood Institute of the NIH for his five-year project studying the remodeling of blood vessels following arterial blockage, “Cellular Reductive State Regulates Arteriogenesis.” This is Dr. Pattillo’s first NIH R01 grant.
“The goal of this NIH-supported five-year study is to determine the levels of antioxidants to drive maximal blood vessel remodeling in response to a vascular blockage, such as peripheral artery disease,” explained Dr. Pattillo.
The gradual occlusion of blood vessels such as that reported in peripheral artery disease is increasing in frequency, due to a variety of risk factors including several cardiovascular pathologies such as diabetes, obesity, etc. This project addresses the novel relationship between the antioxidant glutathione, its oxidized form (GSSG) and the protein modifications (glutathionylation) that influence the progression of arteriogenesis following the occlusion of conduit arteries. The proposed research will uncover the underlying mechanisms by which levels of glutathione and corresponding protein modification can be manipulated to enhance the progression of arteriogenesis following ischemic insult; providing potential avenues to the development of novel vascular therapeutics.
Successful completion of this project will provide new insights into the mechanism by which glutathione regulates arteriogenesis in a physiologic range of GSH:GSSG following arterial ligation. Such information could be the basis for new intervention therapies developed to precisely control arteriogenesis following artery blockage. Enhancing the vascular remodeling potential of tissue through manipulation of glutathione and protein glutathionylation may represent a critical first step in reducing tissue damage due to vascular occlusion.
Dr. Pattillo is the Principle Investigator of the project. A. Wayne Orr, PhD, Professor and Director of the Research Division in the Department of Pathology and an expert in shear mediated endothelial biology, is a co-investigator.