Abstract 2374: Pioglitazone Attenuates Angiotensin Ii-Induced Cardiac Hypertrophy and Fibrosis Through Stimulation of Adiponectin Secretion
A recent clinical trial, PROactive, demonstrated that peroxisome proliferators-activated receptor γ ligand, pioglitazone improved cardiovascular outcome in patients with type II diabetes. The favorable metabolic effects in patients treated with pioglitazone are also associated with increase in plasma adiponectin. However, the role of adiponectin in the therapeutic effects of pioglitazone remains unclear. Here, we investigated whether pioglitazone can attenuate angiotensin II-induced cardiac hypertrophy, and if so, to elucidate the role of adiponectin in its cardioprotective effects. Wild-type (WT) mice or adiponectin deficient (APN-KO) mice were divided into four groups as fellow. (1) control mice, (2) mice treated with pioglitazone, (3) angiotensin II-infused mice, (4) angiotensin II-infused mice treated with pioglitazone. Mice were treated with pioglitazone as food admixture at a concentration of 0.01%. One week later, mice were infused with angiotensin II at 3.2mg/kg/d for 2 weeks. In WT mice subjected to the Ang II infusion, cardiac hypertrophy and fibrosis developed after 2 weeks. In mice treated with pioglitazone, cardiac hypertrophy was significantly attenuated as estimated by heart weight-to-body weight ratio (P < 0.05), cardiomyocyte area (P < 0.05), and echocardiographic measurements (P < 0.05), whereas treatment with pioglitazone did not affect systolic blood pressure. Treatment with pioglitazone also reduced angiotensin II-induced cardiac fibrosis (P < 0.05). Significant increase of plasma adiponectin levels was observed in WT mice treated with pioglitazone (P < 0.01). Finally, treatment with pioglitazone did not affect angiotensin II-induced cardiac hypertrophy and fibrosis in APN-KO mice. We demonstrate that pioglitazone could attenuate angiotensin II-induced cardiac hypertrophy and fibrosis probably through stimulation of adiponectin secretion. These data provide the direct evidence that adiponectin plays an essential role in the cardioprotective effects of pioglitazone.