Regional Differences In Integrin Expression - Role Of Alpha(5)Beta(1) In Regulating Smooth Muscle Cell Functions

There is increasing evidence to suggest that coronary smooth muscle cells (SMCs) differ from noncoronary SMCs, As integrin adhesion molecules regulate many SMC functions, we hypothesized that differences in integrin expression on coronary and noncoronary SMCs may account for cellular differences. Analysis of integrin expression on freshly isolated porcine coronary and noncoronary SMCs revealed that coronary SMCs express significantly less alpha (5)beta (1) than noncoronary SMCs, whereas the expression of total beta (1) and that of alpha (v)beta (3) are similar. Consistent with these findings, coronary SMCs demonstrated significantly less adhesion to fibronectin, compared with carotid artery SMCs. As alpha (5)beta (1)-mediated signaling has been associated with cellular proliferation, the effects of differential alpha (5)beta (1) expression on cell proliferation were examined by comparing primary coronary and carotid artery SMC proliferation. Coronary SMC growth was significantly lower than that of carotid artery SMCs when plated on fibronectin or type I collagen. Blocking alpha (5)beta (1) function on carotid artery SMCs produced a significant decrease in cellular proliferation, resulting in growth similar to that of coronary SMCs. Furthermore, blocking alpha (5)beta (1), but not alpha (v)beta (3), inhibited loss of ar-smooth muscle actin in proliferating SMCs, Proliferating coronary SMCs were found to upregulate alpha (5)beta (1) expression, further indicating a role for alpha (5)beta (1) in SMC growth. These results suggest that dissimilar alpha (5)beta (1) integrin expression may mediate regional differences in phenotype of vascular SMCs.