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: Yoichiro Hirata, Michio Shimabukuro, Etsuko Uematsu, Takeshi Soeki, Hirotsugu Yamada, Yoshiki Sakai, Mizuho Nakayama, Kunio Matsumoto, Takashi Igarashi, Masataka Sata
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 674 Issue 2-3 Pg. 352-8 (Jan 15 2012) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 22094066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Delayed-Action Preparations
• Enzyme Inhibitors
• Pyridines
• ONO 1301
• Hepatocyte Growth Factor
• Epoprostenol
• Thromboxane-A Synthase

Topics

• Animals
• Delayed-Action Preparations
• Enzyme Inhibitors (chemical synthesis, pharmacology, therapeutic use)
• Epoprostenol (agonists)
• Fibrosis
• Heart (drug effects, physiopathology)
• Hepatocyte Growth Factor (metabolism)
• Male
• Myocardium (metabolism, pathology)
• Neovascularization, Physiologic (drug effects)
• Pyridines (chemical synthesis, pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Thromboxane-A Synthase (antagonists & inhibitors)