α8β1 integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium

Abstract

Integrins mediate cell attachment to the extracellular matrix (ECM) regulating migration, proliferation, and differentiation. We previously reported the presence of α8β1 integrin on cultured cardiac fibroblasts. Extending this information, we localized α8β1 integrin in normal rat myocardial tissue, and investigated its expression pattern in rats chronically infused with angiotensin II (Ang II, 500 ng/kg/min), a well-recognized profibrotic factor. α8β1-integrin expression was analyzed by binding assay, western blotting, and immunohistochemistry. In normal myocardium, immunohistochemical staining for α8 was found in fibroblasts, as well as in the epicardium, endocardium, and valves. Vascular smooth muscle cells (VSMCs) of the media of cardiac arteries also stained positively. After 14-d-Ang II infusion, staining for fibronectin, as well as collagen staining by Sirius red, revealed extensive interstitial and perivascular fibrosis. Increased expression of α8 integrin in ventricular smooth muscle (SM) α-actin-positive fibroblasts (myofibroblasts) was also recorded. The upregulation of α8β1 integrin was confirmed by binding assay and by western blotting. Microscopic scars, a characteristic of reparative fibrosis, were invaded by matrix proteins and by strongly α8- and SM α-actin-positive myofibroblasts. The results indicate that, in rat adult myocardium, α8β1 integrin is expressed in fibroblasts and VSMC. In Ang II-infused animals, α8β1-integrin expression was enhanced in the left ventricle and arteries. The coordinate regulation of α8β1 integrin on fibroblasts and ECM proteins raises the possibility that this integrin is implicated in the deposition of matrix components leading to fibrosis.