Temporal response and localization of integrins beta1 and beta3 in the heart after myocardial infarction: regulation by cytokines.

Abstract

BACKGROUND:

Integrins are involved in structural remodeling and tissue repair. This study aimed to elucidate the role of the beta-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 beta1 and beta3 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 beta1 and beta3 gene expression and protein production were low in sham-operated hearts. After MI, the beta1 and beta3 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 beta1A localized primarily in fibroblasts and inflammatory cells, beta1D localized in myocytes, and integrin beta3 was associated primarily with endothelial and smooth muscle cells in peri-infarct vessels. In cultured myocytes, there was isoform transition from the adult beta1D to the fetal beta1A on exposure to TNF-alpha. This was confirmed in vivo in the peri-infarct myocytes, but the transition was voided in TNF-/--knockout mice.

CONCLUSIONS:

Integrins beta1 and beta3 are significantly activated in the infarcted myocardium. Integrin beta1 is active particularly at sites of inflammation and fibrosis, whereas integrin beta3 localizes to vessels in the peri-infarct zone in a temporally coordinated manner. Integrin beta1D to beta1A isoform transition in myocytes is regulated by TNF-alpha.

• Authors: Mei Sun, M Anne Opavsky, Duncan J Stewart, Marlene Rabinovitch, Fayez Dawood, Wen-Hu Wen, Peter P Liu
• Journal: Circulation (Circulation) Vol. 107 Issue 7 Pg. 1046-52 (Feb 25 2003) ISSN: 1524-4539 [Electronic] United States
• PMID: 12600920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin beta1
• Integrin beta3
• Protein Isoforms
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Gene Expression Regulation (drug effects)
• Immunohistochemistry
• In Situ Hybridization
• Integrin beta1 (analysis, biosynthesis, genetics)
• Integrin beta3 (analysis, biosynthesis, genetics)
• Kinetics
• Male
• Myocardial Infarction (genetics, metabolism, pathology)
• Myocardium (chemistry, metabolism)
• Protein Isoforms (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Transcription, Genetic
• Tumor Necrosis Factor-alpha (pharmacology)