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Title: Exploring the difference in the mechanics of vascular smooth muscle cells from wild type and apolipoprotein-E knockout mice
Atherosclerosis-related cardiovascular diseases are a leading cause of mortality worldwide. Vascular smooth muscle cells (VSMCs) comprise the medial layer of the arterial wall and undergo phenotypic switching during atherosclerosis to a synthetic phenotype capable of proliferation and migration. The surrounding environment undergoes alterations in extracellular matrix (ECM) stiffness and composition in addition to an increase in addition to an increase in cholesterol content. Using an atherosclerotic murine model, we analyzed how the mechanics of VSMCs isolated from western diet fed apolipoprotein-E knockout (ApoE -/- ) and wild type (WT) mice were altered during atherosclerosis. Increased stiffness of ApoE -/- VSMCs correlated with a greater degree of stress fiber alignment as evidenced by atomic force microscopy (AFM)-generated force maps and stress fiber topography images. On type-1 collagen (COL1)-coated polyacrylamide (PA) gels of varying stiffness, WT VSMCs had higher adhesion forces to N-Cadherin (N-Cad) and COL1. ApoE -/- VSMC stiffness was significantly greater than WT cells with increased cell stiffness with increasing substrate stiffness for both ApoE -/- and WT VSMCs . In addition, ApoE -/- VSMCs showed an enhanced migration capability on COL1-coated substrates and a general decreasing trend in migration capacity with increasing substrate stiffness, correlating with the lower adhesion forces as compared to WT VSMCs. Altogether, these results demonstrate the potential contribution of the alteration in VSMC mechanics in the development of atherosclerosis.  more » « less
Award ID(s):
2127031 2304667
NSF-PAR ID:
10358021
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
American Journal of Physiology-Cell Physiology
ISSN:
0363-6143
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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