Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with aging in mice on WD. Total collagen content increased significantly with age in mice fed WD. We compared expression of endothelial nitric oxide synthase and acetylcholine-mediated nitric oxide release but found no evidence of endothelial dysfunction in older mice. Time-averaged volumetric blood flow in all groups showed no significant changes. Wire myography of aortic rings revealed decreases in active stress generation with agemore »
This content will become publicly available on September 28, 2023
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 more »
- Publication Date:
- NSF-PAR ID:
- 10358021
- Journal Name:
- American Journal of Physiology-Cell Physiology
- ISSN:
- 0363-6143
- Sponsoring Org:
- National Science Foundation
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