Infarction : Regulation by Cytokines 3 in the Heart After Myocardial β 1 and β Temporal Response and Localization of Integrins

Background—Integrins are involved in structural remodeling and tissue repair. This study aimed to elucidate the role of the &bgr;-integrins in cardiac remodeling after myocardial infarction (MI). Methods and Results—The MI model was created by ligation of the left anterior descending coronary artery in rats. We detected cardiac integrins &bgr;1 and &bgr;3 gene expression (quantitative in situ hybridization) and protein production (Western blot and immunohistochemistry) and potential regulation by tumor necrosis factor (TNF) using neonatal ventricular myocytes and TNF−/− knockout mice. Integrins &bgr;1 and &bgr;3 gene expression and protein production were low in sham-operated hearts. After MI, the &bgr;1 and &bgr;3 mRNA and proteins were significantly increased at the site of MI at day 3, reached a peak at day 7, and gradually declined thereafter. Integrin &bgr;1A localized primarily in fibroblasts and inflammatory cells, &bgr;1D localized in myocytes, and integrin &bgr;3 was associated primarily with endothelial and smooth muscle cells in peri-infarct vessels. In cultured myocytes, there was isoform transition from the adult &bgr;1D to the fetal &bgr;1A on exposure to TNF-&agr;. This was confirmed in vivo in the peri-infarct myocytes, but the transition was voided in TNF−/−-knockout mice. Conclusions—Integrins &bgr;1 and &bgr;3 are significantly activated in the infarcted myocardium. Integrin &bgr;1 is active particularly at sites of inflammation and fibrosis, whereas integrin &bgr;3 localizes to vessels in the peri-infarct zone in a temporally coordinated manner. Integrin &bgr;1D to &bgr;1A isoform transition in myocytes is regulated by TNF-&agr;.

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