Related Experiment Video
Updated: Jul 8, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Up-regulation of PPARgamma in myocardial infarction
Daniela Fliegner1, Dirk Westermann, Alexander Riad
1Cardiovascular Disease in Women, Charité, Center for Cardiovascular Research, Charité, University of Medicine Berlin, Germany.
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.
Insights
Myocardial infarction (MI) increases peroxisome proliferator-activated receptor gamma (PPARγ) but decreases metabolic genes. Angiotensin receptor blockers (ARBs) like irbesartan improved cardiac function and upregulated fatty acid oxidation enzymes post-MI.
Area of Science:
- Cardiology
- Molecular Biology
- Metabolic Regulation
Background:
- Peroxisome proliferator-activated receptors (PPARs) are crucial for cardiac energy metabolism, especially following myocardial injury.
- The role of PPARs in myocardial infarction (MI) and the potential modulation by angiotensin receptor blockers (ARBs) warrant investigation.
Purpose of the Study:
- To investigate the regulation of PPARs (alpha, beta/delta, gamma) in a rat model of MI.
- To determine the effect of the ARB, irbesartan, on PPAR expression and activity post-MI.
- To assess the impact on PPAR target genes and cardiac function.
Main Methods:
- Induction of MI in male rats, followed by three weeks of treatment with placebo or irbesartan.
- Measurement of PPAR protein and gene expression, including target genes and glucose transporters.
- Analysis of cardiac function (LVP, dp/dtmax, LVEDP) and PPARgamma localization via immunofluorescence.
Main Results:
- MI impaired cardiac function, which was improved by irbesartan.
- PPARalpha and PPARbeta/delta expression remained unchanged post-MI and with irbesartan treatment.
- PPARgamma expression increased in the infarcted area, correlating with increased CTGF, while PPAR target genes decreased. Irbesartan upregulated CD36 and ACO in non-infarcted areas.
Conclusions:
- Endogenous PPARgamma upregulation in MI is insufficient to overcome reduced metabolic gene expression and is associated with profibrotic mediator CTGF.
- Irbesartan enhances fatty acid oxidation post-MI through mechanisms independent of PPARgamma regulation.
