Cross‐talk between Angiotensin II and IGF‐1‐induced connexin 43 expression in human saphenous vein smooth muscle cells involving αvβ3 integrin clustering and activation of focal adhesion kinase

Abstract

Vascular restenosis following coronary artery bypass grafts is a major clinical complication due to intimal hyperplasia in venous conduits. However, the precise underlying mechanisms of intimal hyperplasia are still unclear. We have recently reported that increased expression of connexin43 (Cx43) is involved in the proliferation of vascular smooth muscle cells (VSMCs) in human saphenous vein (SV). In this study, we investigated the signaling transduction pathway involved in Cx43 expression and SV SMC proliferation. Angiotensin‐II (AT‐II, 100ng/ml) increased AT‐1R mRNA expression and IGF‐1 (100ng/ml) upregulated IGF‐1R mRNA expression in SV SMCs. Interestingly, AT‐1R expression was also increased by IGF‐1 treatment and IGF‐1R expression was increased by AT‐II treatment. Both AT‐II and IGF‐1 significantly induced the expression of αvβ3 integrin and downstream activation of FAK in SV SMCs. AT‐II and IGF‐1 also significantly induced the expression of Cx43 in SV SMCs. The effect of AT‐II and IGF‐1 on Cx43 expression was attenuated by AT‐1 receptor antagonist, Losartan, IGF‐1R blocking antibody and αvβ3 integrin antibody. These data demonstrate a cross‐talk between IGF‐1R and AT‐1 in AT‐II and IGF‐1‐induced Cx43 expression in SV SMCs involving αvβ3 integrin clustering and downstream activation of FAK signaling pathway.(Supported by a grant from the NIH R01HL07349)