title: 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.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-city, Tokushima 770-8503, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.forename: Etsuko
authors.initials: E
authors.lastname: Uematsu
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamada
authors.forename: Daiju
authors.initials: D
authors.lastname: Fukuda
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009218:Myosins / Q000276:immunology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000378:metabolism
chemical_list: D011725:Pyridines; D020097:Natriuretic Peptide, Brain; C105488:ONO 1301; D009218:Myosins