Peroxisome Proliferator-Activated Receptor β/δ Activation Improves Angiotensin II-Induced Cardiac Hypertrophy in Vitro

Agonists of the peroxisome proliferator-activated receptor alpha (PPARα) and gamma (γ) exert anti-proliferative and anti-inflammatory effects that led to the testing of these drugs in experimental cardiac hypertrophy. However, the effect of PPAR beta/delta (β/δ) agonists in hypertrophy is not yet known. In this paper, an experiment was conducted to explore whether PPARβ/δ activation has an effect on cardiac hypertrophy. An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with Angiotensin II (Ang II1μmol·L−1) stimulation. For the examination of PPAR β/δ effect, the cultured rat cardiac myocytes were pretreated with GW0742 (10μmol·L−1), an agonist of PPARβ/δ, for 48h before Ang II stimulation. The following parameters in the cultured cells were determined: surface areas of myocytes were measured by the NIH Image Software; 3H-leucine incorporation into myocytes was counted by liquid scintillometer; mRNA expression of PPARβ/δ, ANP, BNP, MMP9, MMP2, and IL-1β was detected by RT-PCR; PPARβ/δ protein expression was evaluated with immunofluorescence staining; GW0742 could ameliorate Ang II-induced cardiomyocyte hypertrophy, as indicated by its inhibitory effects on the surface area of myocytes, and ANP and BNP mRNA expressions in myocytes and 3H-leucine incorporation into myocytes. Meanwhile, GW0742 pretreatment exerted inhibition on mRNA expression augmentation of such cytokines as MMP9, MMP2, and IL-1β in hypertrophic myocytes. In addition, the down-regulated expression of PPARβ/δ mRNA and protein in hypertrophic myocytes was also significantly reversed by GW0742. We demonstrate for the first time that GW0742 exerts a beneficial effect on Ang II-induced cardiac hypertrophy and the relation to inflammation response.

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