Arterial aging is associated with decreased arterial contractility and altered mechanosensitive response to external stimuli in vascular smooth muscle cells. This study investigates the effect of extracellular matrix and substrate stiffness on integrin-mediated cell adhesion and actin cytoskeleton in aged cells. Vascular smooth muscle cells were isolated from soleus feed arteries from young (4 months) and old (24 months) male Fischer 344 rats. Then, cells were plated on rigid or soft substrates functionalized with matrix proteins (fibronectin and collagen I), stained for beta-1 integrin and smooth muscle alpha-actin, and imaged using confocal microscopy. Quantitative analysis of fluorescence images showed that overall integrin expression for young and old cells is the same on soft but not on rigid substrates. In addition, integrin beta-1 subunit pairs with integrin alpha-5 subunit to bind fibronectin and with integrin alpha-2 subunit to bind collagen, thus, overall integrin expression is matrix dependent on either substrate. Fluorescence intensity measurements of overall alpha-actin expression is matrix-dependent in old cells plated on rigid substrates, with no change for soft substrates. However, young cells present an opposite behavior, such that overall actin expression on soft substrates is matrix dependent. These data suggest that beta-1 integrin expression and alpha-actin cytoskeleton are differentially modulated by matrix and substrate stiffness in aging.

Dysregulation of integrin function and actin cytoskeleton in aged vascular smooth muscle cells

ACS Spring 2022

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