Membrane Cholesterol Interactions with Proteins in Hypercholesterolemia-Induced Endothelial Dysfunction

• Published in: Current atherosclerosis reports 2023-09, Vol.25 (9), p.535-541
• Main Authors: Fancher, Ibra S., Levitan, Irena
• Format: Article
• Language: English
• Subjects: Angiology; Cardiology; Cell Membrane - metabolism; Cholesterol - metabolism; Endothelium, Vascular - physiopathology; Humans; Hypercholesterolemia - metabolism; Medicine; Medicine & Public Health; Potassium Channels, Inwardly Rectifying - metabolism; Topical Collection on Vascular Biology
• ISSN: 1523-3804; 1534-6242
• DOI: 10.1007/s11883-023-01127-w

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.