Abstract 2064: Identifying A Novel Protein Protecting Against Atherosclerosis And Vascular Dysfunction

Abstract

Atherosclerosis and ischemic heart disease are the leading causes of death in the US. The onset of atherosclerosis begins with endothelial dysfunction and ultimately progresses to occlusive plaques by mechanisms that are still incompletely understood. The basic mechanisms of atherosclerosis involve lipid accumulation and immune activation in the vascular wall. These processes are highly regulated, poorly understood, and lead to inflammation and atherosclerotic plaques in the arterial wall. We recently identified that Fat-Specific Protein 27 (FSP27) plays an important role in regulating vascular function. Using both clinical approaches that involved human biospecimens and “humanized” murine models of endothelium-specific FSP27-overexpressing transgenic (E-FSP27tg) mice, we demonstrated that FSP27 protects against high-fat diet (HFD)-induced dyslipidemia, endothelial dysfunction, and vasomotor impairment. We next hypothesized that FSP27 plays a critical role in protecting against atherosclerosis primarily via its action on endothelial cells. To test our hypothesis, we generated an innovative mouse model expressing the human FSP27 transgene specifically in the vascular endothelial cells of atherosclerosis-prone Apoe -/- mice, Apoe -/- -E-FSP27tg. Our preliminary data show that high-fat-high-cholesterol fed Apoe -/- -E-FSP27tg mice are strongly protected against plaque formation in numerous vascular territories including carotids and aorta upon feeding high-fat, high-cholesterol diets. Mechanistically, we found that FSP27 protects against oxidative stress and inflammation in the endothelial cells. Overall, our study discovered the novel beneficial cardiovascular effects of FSP27 where it protects against the development of vascular dysfunction, inflammation, and atherosclerosis.