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Up-regulation of PPARgamma in myocardial infarction

Item Type:Article
Title:Up-regulation of PPARgamma in myocardial infarction
Creators Name:Fliegner, D. and Westermann, D. and Riad, A. and Schubert, C. and Becher, E. and Fielitz, J. and Tschope, C. and Regitz-Zagrosek, V.
Abstract:BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are key regulators for cardiac energy metabolism after myocardial injury. We hypothesized, that PPARs are regulated in myocardial infarction (MI) and their activity is modulated by angiotensin receptor blockers (ARBs). METHODS: Following induction of MI, male rats were treated with placebo or the ARB irbesartan for three weeks. PPARalpha, beta/delta and gamma protein expression and gene expression of PPAR target genes and glucose transporters were measured. PPARgamma-protein expression was analyzed by immunofluorescence. RESULTS: MI decreased LVP and dp/dtmax and increased LVEDP, this effect was counteracted by irbesartan. PPARalpha and PPARbeta/delta protein expression was not altered in MI and was not affected by irbesartan. PPARgamma protein content was increased in the infarcted area and localized to cardiac myocytes and fibroblasts. In parallel, expression of CTGF was increased 10-fold in the infarcted zone. PPAR target genes (CD36, MCAD, ACO and GLUT4) were significantly decreased in infarcted tissue, and this was unaffected by irbesartan. However, CD36 and ACO in the non-infarcted areas were up-regulated by irbesartan. CONCLUSION: Endogenous up-regulation of PPARgamma in MI is insufficient to counteract the decrease in metabolic genes, but parallels an increase in the profibrotic mediator CTGF. Irbesartan increases fatty acid oxidating enzymes after MI independent of PPARgamma regulation.
Keywords:Myocardial infarction, PPARs, Myocardial metabolism, Angiotensin receptor blockers (ARBs), Fibrosis
Source:European Journal of Heart Failure
ISSN:1388-9842
Publisher:Elsevier (The Netherlands)
Volume:10
Number:1
Page Range:30-38
Date:January 2008
Official Publication:https://doi.org/10.1016/j.ejheart.2007.11.005
PubMed:View item in PubMed

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