Kim, Mi-KyoungPark, Hyun-JooKim, Su-RyunChoi, Yoon KyungBae, Soo-KyungBae, Moon-Kyoung2015-08-032015Kim, Mi-Kyoung, Hyun-Joo Park, Su-Ryun Kim, Yoon Kyung Choi, Soo-Kyung Bae, and Moon-Kyoung Bae. 2015. “Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells.” The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology 19 (4): 327-334. doi:10.4196/kjpp.2015.19.4.327. http://dx.doi.org/10.4196/kjpp.2015.19.4.327.1226-4512http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820926The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin-A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.en-USOrexin-AHeme oxygenase-1AngiogenesisVascular endothelial cellsJournal Article2015-08-0310.4196/kjpp.2015.19.4.327