Shear Stress Regulates ABCA1-dependent Membrane Cholesterol Content in Endothelial Cells Facilitating H2S-dependent Vasodilation

Abstract

Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell-cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family a1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner.

Hypothesis: SS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H ₂ S-mediated vasodilation.

Methods: The effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague-Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H ₂ S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content.

Results: SS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H ₂ S-induced vasodilation.

Conclusion: SS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.