Absence of PPARalpha in mice subjected to 28 days of transverse aortic constriction aggravated cardiac hypertrophy and depressed LV ejection fraction compared to wild-type mice.
Does the absence of PPARalpha aggravate the cardiac hypertrophic response to pressure overload in mice?
The absence of PPARalpha exacerbates cardiac hypertrophy and dysfunction in response to pressure overload, suggesting PPARalpha has protective effects during cardiac remodeling.
AIMS: Peroxisome proliferator-activated receptor-alpha (PPARalpha) 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 PPARalpha modulates cardiac remodelling. Accordingly, in this study the hypothesis was tested that the absence of PPARalpha aggravates the cardiac hypertrophic response to pressure overload. METHODS AND RESULTS: Male PPARalpha-/- 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 PPARalpha-/- 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 PPARalpha-/- mice. Moreover, after TAC mRNA levels of hypertrophic (atrial natriuretic factor, alpha-skeletal actin), fibrotic (collagen 1, matrix metalloproteinase-2), and inflammatory (interleukin-6, tumour necrosis factor-alpha, cyclo-oxygenase-2) marker genes were higher in PPARalpha-/- 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 PPARalpha-/- mice, but were not further compromised by TAC. CONCLUSION: The present findings show that the absence of PPARalpha 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 PPARalpha exerts salutary effects during cardiac hypertrophy.
Smeets et al. (Thu,) conducted a other in Pressure overload-induced cardiac hypertrophy. PPARalpha knockout (PPARalpha-/-) vs. Wild-type mice was evaluated on Cardiac hypertrophic response to pressure overload (ventricular weight, LV wall thickness, and cardiac function). Absence of PPARalpha in mice subjected to 28 days of transverse aortic constriction aggravated cardiac hypertrophy and depressed LV ejection fraction compared to wild-type mice.