Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat

• Published in: Cardiovascular research Vol. 64; no. 1; pp. 115 - 124
• Main Authors: SANDHU, Reena, TEICHERT-KULISZEWSKA, Krystyna, NAG, Sukriti, PROTEAU, Gerald, ROBB, Malcolm J, CAMPBELL, Andrew I. M, KULISZEWSKI, Michael A, KUTRYK, Michael J. B, STEWART, Duncan J
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2004
• Subjects: Angiopoietin-1 - analysis; Angiopoietin-1 - genetics; Angiopoietin-1 - metabolism; Angiopoietin-2 - analysis; Angiopoietin-2 - genetics; Angiopoietin-2 - metabolism; Animals; Biological and medical sciences; Blotting, Northern - methods; Blotting, Western - methods; Cardiology. Vascular system; Coronary heart disease; Endothelium, Vascular - chemistry; Endothelium, Vascular - metabolism; Gene Expression Regulation; Heart; Immunohistochemistry - methods; Male; Medical sciences; Myocardial Infarction - metabolism; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Neovascularization, Pathologic; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptor, TIE-2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Myocardial infarction; Rat; Endothelial receptors; Rodentia; Cardiovascular disease; Myocardial disease; Coronary heart disease; Angiogenesis; Vertebrata; Regulation(control); Mammalia; Ischemia; Animal; Infarction; Growth factors; Growth factor; Biological receptor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2004.05.013

This study sought to characterize changes in the angiopoietin system in a rat model of myocardial infarction (MI). Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) bind to the endothelial-specific receptor tyrosine kinase, TIE-2. Ang-2 has been suggested to be an antagonist of TIE-2, possibly acting to release endothelial cells from the tonic stabilizing influence of Ang-1. However, on prolonged exposure, Ang-2 has been shown to acquire agonistic activity at TIE-2, raising the possibility that this isoform may play a direct role in neovascularization. Sprague-Dawley rats were subjected to left coronary ligation and myocardial tissues were harvested from the infarct and peri-infarct regions, or from non-infarcted myocardium. Changes in gene expression were determined by RT-PCR and confirmed by Northern analysis. Changes in protein expression were confirmed by Western analysis and immunocytochemistry, and TIE-2 activity was determined by immunoprecipitation with anti-TIE-2 and antiphosphotyrosine immunoblotting. At 24 h, Ang-1 mRNA and protein expression within the infarct and peri-infarct regions were decreased compared to non-infarcted myocardium, whereas Ang-2 mRNA levels were markedly increased and TIE-2 expression was unchanged. Immunohistochemical staining revealed Ang-1 and TIE-2 immunoreactivity localized to vascular endothelium. In the infarct territory, Ang-2 immunostaining was localized primarily to invading leukocytes at 24 h. At 1 week, Ang-1 expression was partially restored, whereas Ang-2 expression remained elevated. At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation. Thus, myocardial ischemia induced by left coronary artery ligation resulted in a sustained increase in Ang-2 expression and a reciprocal decrease in Ang-1, consistent with a predominant role for Ang-2 in the angiogenic response to MI.