Upregulation of endothelial DRP1 promotes a pathological vasodilation mechanism in response to flow-induced dilation

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Gutierrez Huerta, Cristhian, Birch, Erin, Hader, Shelby, LeBlanc, Amanda, Guterrman, David, Beyer, Andreas
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5732875

Abstract only Background: Endothelial microvascular dysfunction is a strong and independent risk factor for coronary artery disease (CAD), and improvements in microvascular function improve rates of survivability. Microvascular endothelium of healthy individuals releases nitric oxide (NO) in response to increased blood flow, while individuals with CAD release mitochondria-derived hydrogen peroxide (H2O2), a reactive oxygen species (ROS) molecule, in response to the same stimulus. Mitochondrial fission, a mitochondrial regulatory mechanism that is mediated by DRP1, is associated with increased ROS production as well as a multitude of cardiometabolic disease including obesity, pulmonary arterial hypertension, and diabetes. Aim: We hypothesize that increased endothelial DRP1 mediates the phenotypic shift in the release of NO to H2O2 in response to increased blood flow in individuals with CAD. Methods & Results: Atrial and adipose tissue was obtained from surgical discard tissue from individuals with and without CAD (non-CAD). Western blot analysis of LV tissue shows increased DRP1 expression in individuals with CAD compared to non-CAD (1.97 to 0.99, N=3-7, p