Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells |
| |
| Authors: | Mi-Kyoung Kim Hyun-Joo Park Su-Ryun Kim Yoon Kyung Choi Soo-Kyung Bae Moon-Kyoung Bae |
| |
| Affiliation: | 1Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.;2Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea.;3Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. |
| |
| 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 |
|
|
