Acetate and Endothelial Pathobiology

The work involves defining and characterizing the unique endothelial metabolic pathway that leads to the generation of cytoplasmic Ac-CoA from acetate and the role this Ac-CoA plays in TGFβ signaling. This will be tested in vitro and in vivo using genetically engineered mice. Additionally, two distinct translational strategies will be tested: a nanoparticle-based EC-specific RNAi delivery and an oral specific inhibitor, to evaluate the effect of suppressing acetate-based Ac-CoA production on the development and progression of atherosclerosis.