Abstract
It has been shown that administration of angiogenic factors can augment collateral growth in ischemic tissues. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) from various cell types. We evaluated therapeutic efficacy of ONO-1301 in rat cardiac ischemia model. Ligation of left anterior descending coronary arteries was performed to 10-week-old Wistar rats, and the slow releasing form of ONO-1301 was administrated subcutaneously 3 days after the ligation (control group and ONO-1301 group). Hemodynamic parameters and plasma BNP levels were significantly improved by ONO-1301. Histological analysis revealed that ONO-1301 suppressed fibrotic changes in the myocardium (27.7±3.1% vs 23.3±3.6%, p<0.01). HGF and c-Met expression in the myocardium was significantly up-regulated by ONO-1301. Beneficial effects of ONO-1301 were abrogated by administration of a neutralizing anti-HGF antibody. These findings indicate that ONO-1301 has cardioprotective effects in the rat ischemic heart model via augmentation of endogenous HGF production.
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