Membrane cholesterol and substrate stiffness co-ordinate to induce the remodelling of the cytoskeleton and the alteration in the biomechanics of vascular smooth muscle cells

Cardiovascular Research
Hanna J SanyourZhongkui Hong

Abstract

Cholesterol not only deposits in foam cells at the atherosclerotic plaque, but also plays an important role as a regulator of cell migration in atherogenesis. In addition, the progression of atherosclerosis leads to arterial wall stiffening, and thus altering the micromechanical environment of vascular smooth muscle cells (VSMCs) in vivo. Our studies aim to test the hypothesis that membrane cholesterol and substrate stiffness co-ordinate to regulate VSMCs biomechanics, and thus potentially regulate VSMCs migration and atherosclerotic plaque formation. Methyl-β-cyclodextrin was used to manipulate membrane cholesterol content in VSMCs isolated from the descending thoracic aorta of male Sprague-Dawley rats and cultured on Type I collagen-coated polyacrylamide gel substrates with varying stiffness. Atomic force microscopy (AFM) was used to determine VSMCs stiffness and integrin-fibronectin (FN) adhesion. The alignment of submembranous actin filaments was visualized with AFM and confocal microscopy. The constriction force of rat aorta was measured ex vivo using a multi-wire myograph system. Our results demonstrated that cholesterol-depletion and substrate-softening induced a significant decrease in VSMCs stiffness and adhesion to FN...Continue Reading

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Citations

Nov 7, 2019·Clinical Hemorheology and Microcirculation·Xianlei SunAndreas Lendlein
Mar 14, 2019·Cardiovascular Research·Steven J Forrester, Kathy K Griendling
Feb 2, 2021·Annals of the New York Academy of Sciences·Kathryn M CitrinYajaira Suárez
Jun 5, 2021·Frontiers in Cell and Developmental Biology·Xiuli MaoYue Zhou

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