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.
Keywords: Angiogenesis, Ang(1-7), cardiac repair, Mas receptor blockade, myocardial infarction, ventricular dysfunction.
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