OBJECTIVE: This study sought to characterize changes in the angiopoietin system in a rat model of myocardial infarction (MI). BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: This study sought to characterize changes in the angiopoietin system in a rat model of myocardial infarction (MI). BACKGROUND: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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Ryanne P Betgem; Guus A de Waard; Robin Nijveldt; Aernout M Beek; Javier Escaned; Niels van Royen Journal: Nat Rev Cardiol Date: 2014-11-18 Impact factor: 32.419
Authors: Christopher Daly; Elizabeth Pasnikowski; Elena Burova; Vivian Wong; Thomas H Aldrich; Jennifer Griffiths; Ella Ioffe; Thomas J Daly; James P Fandl; Nick Papadopoulos; Donald M McDonald; Gavin Thurston; George D Yancopoulos; John S Rudge Journal: Proc Natl Acad Sci U S A Date: 2006-10-09 Impact factor: 11.205
Authors: Neil P Fam; Sara Arab; Filio Billia; Robin Han; Gerald Proteau; David Latter; Lee Errett; Daniel Bonneau; Rosemary Dunne; Peter P Liu; Duncan J Stewart Journal: Can J Cardiol Date: 2010 Aug-Sep Impact factor: 5.223
Authors: K Rychli; C Kaun; P J Hohensinner; G Rega; S Pfaffenberger; E Vyskocil; J M Breuss; A Furnkranz; P Uhrin; J Zaujec; A Niessner; G Maurer; K Huber; J Wojta Journal: J Thromb Haemost Date: 2009-12-17 Impact factor: 5.824
Authors: Susan M Dallabrida; Nesreen S Ismail; Elke A Pravda; Emily M Parodi; Renee Dickie; Ellen M Durand; Jean Lai; Flavia Cassiola; Rick A Rogers; Maria A Rupnick Journal: FASEB J Date: 2008-05-23 Impact factor: 5.191
Authors: Swathi Balaji; Nate Han; Chad Moles; Aimen F Shaaban; Paul L Bollyky; Timothy M Crombleholme; Sundeep G Keswani Journal: Surgery Date: 2015-09 Impact factor: 3.982