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(Circulation. 2003;107:1046.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Temporal Response and Localization of Integrins ß1 and ß3 in the Heart After Myocardial Infarction

Regulation by Cytokines

Mei Sun, MD, PhD; M. Anne Opavsky, MD, PhD; Duncan J. Stewart, MD; Marlene Rabinovitch, MD; Fayez Dawood, DVM; Wen-Hu Wen, MD; Peter P. Liu, MD

From the Heart and Stroke/Richard Lewar Centre of Excellence and Division of Cardiology, University Health Network (M.S., F.D., W.-H.W., P.P.L); Research Institute, The Hospital for Sick Children (M.A.O., M.R.); and Division of Cardiology, St Michael’s Hospital (D.J.S.), University of Toronto, Canada.

Correspondence to Dr Peter Liu, Heart and Stroke/Richard Lewar Centre of Excellence, EN12-324, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. E-mail peter.liu{at}utoronto.ca

Background— Integrins are involved in structural remodeling and tissue repair. This study aimed to elucidate the role of the ß-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 ß1 and ß3 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 ß1 and ß3 gene expression and protein production were low in sham-operated hearts. After MI, the ß1 and ß3 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 ß1A localized primarily in fibroblasts and inflammatory cells, ß1D localized in myocytes, and integrin ß3 was associated primarily with endothelial and smooth muscle cells in peri-infarct vessels. In cultured myocytes, there was isoform transition from the adult ß1D to the fetal ß1A on exposure to TNF-. This was confirmed in vivo in the peri-infarct myocytes, but the transition was voided in TNF^-/--knockout mice.

Conclusions— Integrins ß1 and ß3 are significantly activated in the infarcted myocardium. Integrin ß1 is active particularly at sites of inflammation and fibrosis, whereas integrin ß3 localizes to vessels in the peri-infarct zone in a temporally coordinated manner. Integrin ß1D to ß1A isoform transition in myocytes is regulated by TNF-.

Key Words: myocardial infarction • integrins • remodeling • angiogenesis • tumor necrosis factor-

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