title: Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat.
abstract: 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.affiliation: Terrence Donnelly Heart Center, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Reena
authors.initials: R
authors.lastname: Sandhu
authors.forename: Krystyna
authors.initials: K
authors.lastname: Teichert-Kuliszewska
authors.forename: Sukriti
authors.initials: S
authors.lastname: Nag
authors.forename: Gerald
authors.initials: G
authors.lastname: Proteau
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Robb
authors.forename: Andrew I M
authors.initials: AI
authors.lastname: Campbell
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuliszewski
authors.forename: Michael J B
authors.initials: MJ
authors.lastname: Kutryk
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
mesh_terms: D042683:Angiopoietin-1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D042702:Angiopoietin-2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2