Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model

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• 作者：Yoichiro Hirata^a ; ^b ; Hirotsugu Kurobe^c ; Etsuko Uematsu^a ; Shusuke Yagi^a ; Takeshi Soeki^a ; Hirotsugu Yamada^a ; Daiju Fukuda^d ; Michio Shimabukuro^d ; Mizuho Nakayama^e ; Kunio Matsumoto^e ; Yoshiki Sakai^f ; Tetsuya Kitagawa^c ; Masataka Sata^a ; ^{sata@clin.med.tokushima-u.ac.jp}
• 关键词：Heart failure ; HGF ; Dilated cardiomyopathy ; Experimental autoimmune myocarditis ; Prostacyclin
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：699
• 期：1-3
• 页码：81-87
• 全文大小：503 K

文摘

Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-induced left ventricle dysfunction in the mouse, rat and pig. Here, we investigated the therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Lewis rats, ONO-1301 (6 mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301. Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partially abrogated by a neutralizing anti-HGF antibody (8 mg/kg/dose). These findings indicate beneficial effects of ONO-1301 in a rat experimental autoimmune myocarditis model.