1. Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model
- Author
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Daiju Fukuda, Hirotsugu Yamada, Shusuke Yagi, Tetsuya Kitagawa, Kunio Matsumoto, Mizuho Nakayama, Michio Shimabukuro, Yoichiro Hirata, Etsuko Uematsu, Yoshiki Sakai, Masataka Sata, Takeshi Soeki, and Hirotsugu Kurobe more...
- Subjects
Cardiomyopathy, Dilated ,Male ,Agonist ,medicine.medical_specialty ,Myocarditis ,Pyridines ,medicine.drug_class ,Cardiomyopathy ,Administration, Oral ,Prostacyclin ,Myosins ,Autoimmune Diseases ,Internal medicine ,Natriuretic Peptide, Brain ,medicine ,Animals ,Pharmacology ,business.industry ,Stem Cells ,Hemodynamics ,Endothelial Cells ,Dilated cardiomyopathy ,medicine.disease ,Brain natriuretic peptide ,Rats ,Disease Models, Animal ,Endocrinology ,Rats, Inbred Lew ,Heart failure ,Hepatocyte growth factor ,business ,medicine.drug - Abstract
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. more...
- Published
- 2013
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