Regular Article
Angiotensin II, Transforming Growth Factor-β1and Repair in the Infarcted Heart

https://doi.org/10.1006/jmcc.1998.0721Get rights and content

Abstract

Tissue repair following myocardial infarction (MI) eventuates in fibrous tissue formation at the site of myocyte necrosis. Following a large transmural MI, fibrosis appears remote to the infarct site. This is associated with extensive tissue remodeling that adversely affects ventricular diastolic function. Substances involved in promoting fibrous tissue formation at MI and remote sites are under investigation. Angiotensin II (AngII), generated at sites of repair, has been implicated. However, its regulatory role on fibrous tissue formation remains uncertain. In the present study we sought to determine whether AngII is correlated to transforming growth factor beta 1 (TGF-β1) expression, a regulator of fibrous tissue formation, at these sites of tissue repair. We studied: (1) localization and expression of angiotensin converting enzyme (ACE), AngII receptors, TGF-β1mRNA and its receptors in the infarcted rat heart; and (2) effect of AngII on TGF-β1synthesis by chronic blockade of AT1receptors began at the time of surgery by losartan in rats with MI. Hearts were studied at 4 weeks post-MI. We found: (1) low-density ACE, AngII and TGF-β1receptor binding and low mRNA for type I collagen and TGF-β1in the normal heart; (2) fibrosis at sites of MI and remote to it, including endocardium and fibrosis of intraventricular septum, interstitial fibrosis of non-infarcted myocardium and fibrosis of visceral pericardium; (3) markedly increased (P<0.01) and colocalized ACE, AngII and TGF-β1receptor binding, type I collagen and TGF-β1mRNA at MI and remote sites of repair; (4) increased TGF-β1concentration (P<0.01) at these sites; and (5) attenuated TGF-β1and type I collagen gene expression (P<0.01) at these sites in rats receiving losartan. These observations suggest locally generated AngII via ATireceptor binding is correlated to TGF-β1expression and synthesis at sites of repair and remote sites in the infarcted rat heart. The mechanism responsible for the role of AngII in TGF-β1remains to be elucidated.

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Please address all correspondence to: Yao Sun, University of Missouri-Columbia, Division of Cardiology, MA432 Medical Sciences Building, Columbia, MO 65212, USA.

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