Peroxisome proliferator-activated receptor-α (PPARα) is a nuclear receptor regulating cardiac metabolism that also has anti-inflammatory properties. Since the activation of inflammatory signalling pathways is considered to be important in cardiac hypertrophy and fibrosis, it is anticipated that PPARα modulates cardiac remodelling. Accordingly, in this study the hypothesis was tested that the absence of PPARα aggravates the cardiac hypertrophic response to pressure overload.

Male PPARα−/− and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days. TAC resulted in a more pronounced increase in ventricular weight and left ventricular (LV) wall thickness in PPARα−/− than in wild-type mice. Compared with sham-operated mice, TAC did not affect cardiac function in wild-type mice, but significantly depressed LV ejection fraction and LV contractility in PPARα−/− mice. Moreover, after TAC mRNA levels of hypertrophic (atrial natriuretic factor, α-skeletal actin), fibrotic (collagen 1, matrix metalloproteinase-2), and inflammatory (interleukin-6, tumour necrosis factor-α, cyclo-oxygenase-2) marker genes were higher in PPARα−/− than in wild-type mice. The mRNA levels of genes involved in fatty acid metabolism (long-chain acyl-CoA synthetase, hydroxyacyl-CoA dehydrogenase) were decreased in PPARα−/− mice, but were not further compromised by TAC.

The present findings show that the absence of PPARα results in a more pronounced hypertrophic growth response and cardiac dysfunction that are associated with an enhanced expression of markers of inflammation and extracellular matrix remodelling. These findings indicate that PPARα exerts salutary effects during cardiac hypertrophy.