Endothelin-1 (ET-1) causes cardiac hypertrophy, and ET receptor antagonists inhibit the development of cardiac hypertrophy in vitro and in vivo. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the family of nuclear receptors, suppresses activator protein-1 (AP-1). We investigated the effects of the thiazolidinediones troglitazone and pioglitazone, activators of PPARγ, on cardiac hypertrophy due to pressure overload provoked by abdominal aortic banding (AB) in rats. Rats were divided into four groups: sham operation with vehicle treatment (n = 5); AB surgery with vehicle treatment (n = 6); AB surgery with troglitazone treatment (100mg·kg-1·day-1; n = 5); and AB surgery with pioglitazone treatment (10mg·kg-1·day-1; n = 8). Treatments were started 7 days before AB surgery, and left ventricular (LV) hypertrophy was assessed 24h after surgery. The ratio of LV weight/body weight (BW) was significantly increased in AB rats compared with sham-operated rats; treatment of AB rats with troglitazone or pioglitazone significantly inhibited the increase in LV weight/BW. Expression of ET-1 mRNA was markedly enhanced in the left ventricles of AB rats; treatment with troglitazone or pioglitazone lowered expression significantly. Suppression of cardiac hypertrophy by pioglitazone treatment was accompanied by a decrease in expression of the gene encoding brain natriuretic factor, a molecular marker for cardiac hypertrophy, in AB rats. Because the ET-1 gene has AP-1 response elements in its 5´-flanking region, the thiazolidinediones troglitazone and pioglitazone may inhibit cardiac hypertrophy partly through suppression of AP-1-induced ET-1 gene up-regulation.
Peroxisome proliferator-activated receptor-γ activators inhibit endothelin-1-related cardiac hypertrophy in rats
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Satoshi SAKAI, Takashi MIYAUCHI, Yoko IRUKAYAMA-TOMOBE, Takehiro OGATA, Katsutoshi GOTO, Iwao YAMAGUCHI; Peroxisome proliferator-activated receptor-γ activators inhibit endothelin-1-related cardiac hypertrophy in rats. Clin Sci (Lond) 1 September 2002; 103 (s2002): 16S–20S. doi: https://doi.org/10.1042/CS103S016S
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