Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells.
10.4196/kjpp.2015.19.4.327
- Author:
Mi Kyoung KIM
1
;
Hyun Joo PARK
;
Su Ryun KIM
;
Yoon Kyung CHOI
;
Soo Kyung BAE
;
Moon Kyoung BAE
Author Information
1. Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 626-870, Korea. mkbae@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
Orexin-A;
Heme oxygenase-1;
Angiogenesis;
Vascular endothelial cells
- MeSH:
Antioxidant Response Elements;
Endothelial Cells*;
Heme Oxygenase-1*;
Human Umbilical Vein Endothelial Cells;
Luciferases;
Tin;
Orexins
- From:The Korean Journal of Physiology and Pharmacology
2015;19(4):327-334
- CountryRepublic of Korea
- Language:English
-
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.
