Effect of pioglitazone on the expression of inflammatory cytokines in attenuating rat cardiomyocyte hypertrophy.

Pioglitazone, one of the synthetic peroxisome proliferator-activated receptor (PPARgamma) agonists, has been found to inhibit inflammatory response. However, it is not known yet whether the preventive effect of pioglitazone on cardiac hypertrophy is related to its antiinflammatory function. The objective of this study was to investigate the role of pioglitazone in attenuation of cardiac hypertrophy and its relation to the inhibitory effect on the inflammatory cytokine expression in cultured neonatal rat cardiomyocytes. The mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), interleukin (IL)-1beta, IL-6, and PPARgamma was measured by using RT-PCR. Cardiomyocyte hypertrophy was induced by stimulating angiotensin II (Ang II) and evaluated both by measuring surface area of cardiac myocyte and 3H-leucine incorporation. The expressions of IL-1beta, IL-6, ANP, and BNP were significantly enhanced, whereas that of PPARgamma was significantly reduced in Ang II-induced hypertrophic cardiomyocytes. Pioglitazone decreased cardiac myocyte surface area and inhibited 3H-leucine incorporation into cardiomyocytes. Furthermore, pioglitazone upregulated the suppressed expression of PPARgamma and attenuated the increased IL-1beta and IL-6 expression. The effect of pioglitazone might be associated with PPARgamma activation and the consequent antiinflammatory function in prevention and treatment of cardiac hypertrophy.