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

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.

• Authors: Yoichiro Hirata, Hirotsugu Kurobe, Etsuko Uematsu, Shusuke Yagi, Takeshi Soeki, Hirotsugu Yamada, Daiju Fukuda, Michio Shimabukuro, Mizuho Nakayama, Kunio Matsumoto, Yoshiki Sakai, Tetsuya Kitagawa, Masataka Sata
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 699 Issue 1-3 Pg. 81-7 (Jan 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23219794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Pyridines
• Natriuretic Peptide, Brain
• ONO 1301
• Myosins

Topics

• Administration, Oral
• Animals
• Autoimmune Diseases (drug therapy, physiopathology)
• Cardiomyopathy, Dilated (drug therapy, physiopathology)
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Hemodynamics (drug effects)
• Male
• Myocarditis (drug therapy, immunology, physiopathology)
• Myosins (immunology)
• Natriuretic Peptide, Brain (blood)
• Pyridines (pharmacology)
• Rats
• Rats, Inbred Lew
• Stem Cells (metabolism)