title: Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells.
abstract: The 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.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea. ; Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea. ; Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Su-Ryun
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
keywords: Angiogenesis; Heme oxygenase-1; Orexin-A; Vascular endothelial cells