Membrane Cholesterol Interactions with Proteins in Hypercholesterolemia-Induced Endothelial Dysfunction

PURPOSE OF REVIEW: The goal of this review is to highlight work identifying mechanisms driving hypercholesterolemia-mediated endothelial dysfunction. We specifically focus on cholesterol-protein interactions and address specific questions related to the impact of hypercholesterolemia on cellular cholesterol and vascular endothelial function. We describe key approaches used to determine the effects of cholesterol-protein interactions in mediating endothelial dysfunction under dyslipidemic conditions. RECENT FINDINGS: The benefits of removing the cholesterol surplus on endothelial function in models of hypercholesterolemia is clear. However, specific mechanisms driving cholesterol-induced endothelial dysfunction need to be determined. In this review, we detail the latest findings describing cholesterol-mediated endothelial dysfunction, highlighting our studies indicating that cholesterol suppresses endothelial Kir2.1 channels as a major underlying mechanism. SUMMARY: The findings detailed in this review support the targeting of cholesterol-induced suppression of proteins in restoring endothelial function in dyslipidemic conditions. The identification of similar mechanisms regarding other cholesterol-endothelial protein interactions is warranted.