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

被引：16
作者：
Kim, Mi-Kyoung [1 ]
Park, Hyun-Joo [1 ,2 ]
Kim, Su-Ryun [1 ,2 ]
Choi, Yoon Kyung [3 ,4 ,5 ]
Bae, Soo-Kyung [2 ]
Bae, Moon-Kyoung [1 ]
机构：
[1] Pusan Natl Univ, Sch Dent, Dept Oral Physiol, Yangsan 626770, South Korea
[2] Pusan Natl Univ, Sch Dent, Dept Dent Pharmacol, Yangsan 626770, South Korea
[3] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA
[4] Massachusetts Gen Hosp East, Dept Neurol, Charlestown, MA 02129 USA
[5] Harvard Univ, Sch Med, Charlestown, MA 02129 USA
来源：
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY | 2015年 / 19卷 / 04期
基金：
新加坡国家研究基金会;
关键词：
Orexin-A; Heme oxygenase-1; Angiogenesis; Vascular endothelial cells; CARBON-MONOXIDE; PROMOTES ANGIOGENESIS; EXPRESSION; PATHWAY; GENE; RATS; NEUROPEPTIDES; HYPOCRETINS; HIF-1-ALPHA; ACTIVATION;
D O I：
10.4196/kjpp.2015.19.4.327
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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.
引用
收藏
页码：327 / 334
页数：8
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