Angiotensin 1-7 promotes cardiac angiogenesis following infarction

Curr Vasc Pharmacol. 2015;13(1):37-42. doi: 10.2174/15701611113119990006.

Abstract

Angiogenesis is central to cardiac repair following myocardial infarction (MI). Cardiac angiotensin converting enzyme (ACE)2 significantly increased postMI, which is coincident with activated angiogenesis. The function of ACE2 is to generate angiotensin (Ang)1-7, an active peptide with cellular actions mediated by Mas receptors. The current study is to determine whether Ang(1-7) is involved in cardiac angiogenesis and facilitates cardiac repair. In the first portion of the study, the temporal expressions of cardiac ACE2 and Mas receptors were detected in rats with MI. In the second portion, MI rats were treated with or without a Mas receptor antagonist, A779 (1mg/kg/day given by minipump) for 7 days. Vascular density and expression of angiogenic mediators in the infarcted myocardium and cardiac function were examined. Compared to controls, ACE2 and Mas receptor levels were significantly increased in the infarcted myocardium for 4 weeks of the observation period. Newly formed vessels were evident in the infarcted myocardium at day 7. Mas receptor blockade significantly reduced vascular density in the infarcted myocardium and impaired ventricular function. In addition, A779 treatment significantly suppressed the cardiac expressions of vascular endothelial growth factor (VEGF)-D and matrix metalloproteinase (MMP)-9 but not expression of other angiogenic mediators, including monocyte Chemoattractant protein (MCP-1), VEGF-C, transforming growth factor (TGF)-β1 and integrin β3. These observations indicate that Ang(1-7) promotes angiogenesis via stimulating the expression of cardiac VEGF-D and MMP-9, thus facilitating cardiac repair and ventricular function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Female
  • Matrix Metalloproteinase 9 / metabolism
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / physiopathology*
  • Neovascularization, Physiologic / physiology*
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / metabolism
  • Vascular Endothelial Growth Factor D / metabolism
  • Ventricular Remodeling / physiology*

Substances

  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Vascular Endothelial Growth Factor D
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • Matrix Metalloproteinase 9
  • angiotensin I (1-7)