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

被引：15

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

页码：327 / 334

页数：8

共 37 条

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