• Li Sheng, Ping Ye, Yong-Xue Liu, Chun-Guang Han, and Zhi-Yi Zhang.
• Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
• Clin. Exp. Hypertens. 2008 Feb 1; 30 (2): 109-19.

AbstractAgonists of the peroxisome proliferator-activated receptor alpha (PPARalpha) and gamma (gamma) 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 (beta/delta) agonists in hypertrophy is not yet known. In this paper, an experiment was conducted to explore whether PPARbeta/delta activation has an effect on cardiac hypertrophy. An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with Angiotensin II (Ang II1micromol x L(-1)) stimulation. For the examination of PPAR beta/delta effect, the cultured rat cardiac myocytes were pretreated with GW0742 (10 micromol.L(-1)), an agonist of PPARbeta/delta, 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; (3)H-leucine incorporation into myocytes was counted by liquid scintillometer; mRNA expression of PPARbeta/delta, ANP, BNP, MMP9, MMP2, and IL-1beta was detected by RT-PCR; PPARbeta/delta 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 (3)H-leucine incorporation into myocytes. Meanwhile, GW0742 pretreatment exerted inhibition on mRNA expression augmentation of such cytokines as MMP9, MMP2, and IL-1beta in hypertrophic myocytes. In addition, the down-regulated expression of PPARbeta/delta 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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