Activation of PPARγ by rosiglitazone inhibits pressure overload‐induced cardiac hypertrophy and improves diastolic dysfunction in mice

Peroxisome proliferator‐activated receptor γ (PPARγ) elicits potent anti‐proliferation and anti‐fibrosis effects in certain tissues and cells. This study investigated the effects of the PPARγ agonist rosiglitazone and antagonist T0070907 in transverse aortic constriction (TAC)‐induced pathologic cardiac remodeling in C57BL6 mice. Male mice were subjected to TAC or sham surgery and treated with rosiglitazone (10 mg/kg), T0070907 (1.5 mg/kg) or vehicle by gavage daily beginning 3 days and continued for 3 weeks after TAC. Cardiac hypertrophy was assessed by the ratio of left ventricular weight to body weight (LVW/BW) or tibia length (LVW/Tibia), diastolic function was determined by measuring LV end‐diastolic pressure (LVEDP) and PPARγ protein level was assessed by Western blotting. LV PPARγ expression was decreased after TAC. Rosiglitazone treatment dramatically attenuated TAC‐induced cardiac hypertrophy and improved diastolic dysfunction; T0070907 had no effects on cardiac hypertrophy, but exacerbated LV diastolic dysfunction compared to vehicle treated TAC mice (Table). Further, in isolated adult mouse cardiac fibroblasts, either rosiglitazone or adenovirus‐mediated PPARγ overexpression significantly inhibited transforming growth factor‐β1‐induced extracellular matrix molecules such as CTGF, periostin and α‐SMA expression. These data suggested that PPARγ agonist has potential to prevent pressure overload‐induced cardiac remodeling.