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http://dx.doi.org/10.4196/kjpp.2015.19.4.327

Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells  

Kim, Mi-Kyoung (Department of Oral Physiology, School of Dentistry, Pusan National University)
Park, Hyun-Joo (Department of Oral Physiology, School of Dentistry, Pusan National University)
Kim, Su-Ryun (Department of Oral Physiology, School of Dentistry, Pusan National University)
Choi, Yoon Kyung (Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School)
Bae, Soo-Kyung (Department of Dental Pharmacology, School of Dentistry, Pusan National University)
Bae, Moon-Kyoung (Department of Oral Physiology, School of Dentistry, Pusan National University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.19, no.4, 2015 , pp. 327-334 More about this Journal
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.
Keywords
Orexin-A; Heme oxygenase-1; Angiogenesis; Vascular endothelial cells;
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