Project Grant R01HL185184

Summary

The University of North Carolina at Chapel Hill received a $618,352 Project Grant award dated July 15, 2026, from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct mechanistic research on endothelial dysfunction and cardiovascular disease. The grant funds a four-year research initiative (through March 31, 2031) investigating how mechanical forces—specifically oscillatory shear stress from disturbed blood flow patterns—regulate lipid metabolism in endothelial cells and contribute to vascular dysfunction. The research will employ molecular, cellular, and in vivo approaches including stable isotope tracing, transgenic mouse models (DGAT1 and ATGL endothelial-specific knockout mice), post-translational protein analyses, and microtubule stability assessments to elucidate the relationship between lipid droplet accumulation, transcription factor regulation (FOXO1), and impaired endothelial barrier function.

The project deliverables consist of hypothesis-driven basic research outputs including scientific findings on how oscillatory shear stress suppresses triglyceride hydrolysis through FOXO1 inactivation and downstream ATGL downregulation, as well as mechanistic characterization of how lipid droplet accumulation disrupts endothelial mechanotransduction and barrier integrity through microtubule destabilization and RhoA pathway activation. These research products will advance understanding of a previously underrecognized metabolic pathway linking fluid mechanical forces to atherosclerosis initiation, potentially informing future therapeutic targets for cardiovascular disease prevention. Work is performed at the University of North Carolina at Chapel Hill campus in Chapel Hill, North Carolina.