© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling
Presented in part at the 72nd Scientific Session of the American Heart Association, Atlanta, GA, USA, November 7–10, 1999, and published in abstract form (Circulation 1999;100(Suppl. 1):562)
Medizinische Klinik, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
d.fraccarollo{at}medizin.uni-wuerzburg.de
* Corresponding author. Present address: Medizinische Universitätsklinik, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. Tel.: +49-931-201-5301; fax: +49-931-201-5302
Objectives: Endothelin A (ETA) receptor blockade started early after myocardial infarction (MI) promotes adverse left ventricular (LV) dilatation. We tested the hypothesis that inhibition of ETA receptors during the early phase of healing affects collagen synthesis and accumulation, and induces expansion of infarcted myocardium. Methods: Starting 3 h after coronary ligation, female Wistar rats were treated with the selective ETA receptor antagonist LU 135252 (30 mg/kg body wt/day) or placebo. A period of 7 days after MI, hemodynamic, morphometric and biochemical studies were performed. Results: ETA receptor blockade enhanced infarct expansion index and decreased LV systolic function. Infarct scar of LU 135252-treated rats displayed decreased gene expression of fibrillar type I/III collagens and of transforming growth factor-β1 (TGF-β1). Collagen content in the infarct scar and border regions was lower after ETA inhibition. In addition, Western blot analysis revealed, after ETA receptor blockade, enhanced matrix metalloproteinases MMP-13, and MMP-2 expression in the infarcted LV myocardium. Conclusions: These data demonstrate that endothelin stimulates collagen accumulation at the site of infarction. Decreased collagen and TGF-β1 gene expression, associated with enhanced infarct expansion and MMP up-regulation likely contributes to ETA receptor blockade–mediated deleterious effects on ventricular remodeling after infarction.
KEYWORDS Endothelins; Extracellular matrix; Gene expression; Infarction; Remodeling
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