The Role of Membrane Cholesterol in Regulating Vascular Function

Endothelial cells (ECs) in resistance arteries express integral membrane proteins, including ion channels and transporters critical for blood flow regulation and intercellular communication. The function of these proteins is highly sensitive to membrane cholesterol content, which can disrupt responses to vasoactive molecules such as nitric oxide, carbon monoxide, and hydrogen sulfide (H₂S). The ATP-binding cassette transporter A1 (ABCA1) regulates membrane cholesterol by promoting efflux to nascent HDL particles. We found that increased ABCA1 expression lowers EC membrane cholesterol, while inhibition raises cholesterol and impairs H₂S-mediated vasodilation. Shear stress (SS) further modulates this system, enhancing ABCA1 expression and reducing membrane cholesterol. Using rat mesenteric arteries and human aortic ECs, we demonstrate that ABCA1 and SS are key determinants of endothelial lipid homeostasis and vasodilatory capacity.