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Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle

Authors :
Krishna Raj Ojha
Song Yi Shin
Samuel Padgham
Frida Leon Olmedo
Bohong Guo
Gang Han
Christopher Woodman
Andreea Trache
Source :
Frontiers in Physiology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin β1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin β1 expression in aging, while soft substrates abolish age-induced differences in overall integrin β1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries.

Details

Language :
English
ISSN :
1664042X and 29099366
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Physiology
Publication Type :
Academic Journal
Accession number :
edsdoj.f0743a6f5cbb42daa64f02e29099366b
Document Type :
article
Full Text :
https://doi.org/10.3389/fphys.2022.913673