Regional Differences in Integrin Expression: Role of &agr;5&bgr;1 in Regulating Smooth Muscle Cell Functions

Abstract— 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 &agr;5&bgr;1 than noncoronary SMCs, whereas the expression of total &bgr;1 and that of &agr;v&bgr;3 are similar. Consistent with these findings, coronary SMCs demonstrated significantly less adhesion to fibronectin, compared with carotid artery SMCs. As &agr;5&bgr;1-mediated signaling has been associated with cellular proliferation, the effects of differential &agr;5&bgr;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 &agr;5&bgr;1 function on carotid artery SMCs produced a significant decrease in cellular proliferation, resulting in growth similar to that of coronary SMCs. Furthermore, blocking &agr;5&bgr;1, but not &agr;v&bgr;3, inhibited loss of &agr;-smooth muscle actin in proliferating SMCs. Proliferating coronary SMCs were found to upregulate &agr;5&bgr;1 expression, further indicating a role for &agr;5&bgr;1 in SMC growth. These results suggest that dissimilar &agr;5&bgr;1 integrin expression may mediate regional differences in phenotype of vascular SMCs.