Regulation of α₇-integrin expression in vascular smooth muscle by injury-induced atherosclerosis

Injury of vascular smooth muscle cells (VSMCs) by allylamine (AAM) leads to phenotypic changes associated with atherogenic progression including increased proliferation, migration, and alterations in cell adhesion. In the present study, the relationship between AAM-induced vascular injury and expression of the α₇-integrin subunit was investigated. The α₇-mRNA and protein expression were examined using real-time RT-PCR, fluorescence-activated cell sorting analysis (FACS), immunohistochemistry, and immunoblotting. In cultured VSMCs from aortas of AAM-treated rats (70 mg/kg for 20 days), α₇-mRNA levels were increased more than twofold compared with control cells. No change was seen in β₁-integrin expression. FACS analysis revealed increased cell surface expression of α₇-protein (25 ± 9%; *P < 0.05). AAM treatment of naive VSMCs enhanced α₇-mRNA expression (2.4 ± 0.7-fold, mean ± SE; *P < 0.05). The increased α₇-mRNA expression was attenuated by the amine oxidase inhibitor semicarbazide and the antioxidant pyrrolidine dithiocarbamate, which confirms a role for oxidative stress in modulating α₇- expression. In vivo α₇-mRNA and protein expression were enhanced in the aortas of AAM-treated rats. In addition, increased α₇-integrin expression facilitated AAM VSMC adhesion to laminin more efficiently compared with control (51 ± 2%; *P < 0.05). Chemical injury induced by AAM significantly enhances α₇- integrin expression in VSMCs. These findings implicate for the first time the expression of α₇-integrin during the response of VSMCs to vascular injury.