title: A synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury.
abstract: ONO-1301, a synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, promotes the production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) by various cell types. Here, we evaluated the therapeutic efficacy of ONO-1301 in rats with ischemia/reperfusion injury. Ligation of the left anterior descending arteries was performed in 10-week-old Wistar rats, and released 30 min later. A slow-release form of ONO-1301 was administered subcutaneously at 3h and 3 weeks after reperfusion injury. Hemodynamic parameters were significantly improved in the ONO-1301 group. Histological analysis revealed that ONO-1301 suppressed ischemic and fibrotic changes in the myocardium (ischemic area, control group: 58.6 ± 8.7% vs. ONO-1301 group: 44.4 ± 5.8%, fibrotic area, 33.5 ± 5.9% vs. 22.3 ± 6.2%, P<0.05, respectively), and enhanced neovascularization in the border zone. HGF expression was up-regulated by ONO-1301. Double-immunostaining revealed that myofibroblasts in the border zone of ischemic myocardium mainly expressed HGF. Our findings suggest that ONO-1301 might have therapeutic potential in treating ischemic heart disease.
authors.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Etsuko
authors.initials: E
authors.lastname: Uematsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamada
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011464:Epoprostenol / Q000819:agonists*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D011725:Pyridines; C105488:ONO 1301; D017228:Hepatocyte Growth Factor; D011464:Epoprostenol; D013930:Thromboxane-A Synthase