Angiogenic role of orexin-A via the activation of extracellular signal-regulated kinase in endothelial cells

作者：Kim Mi Kyoung; Park Hyun Joo; Kim Su Ryun; Choi Yoon Kyung; Shin Hwa Kyoung; Jeon Jae Hoon; Jang Hye Ock; Yun Il; Bae Soo Kyung; Bae Moon Kyoung^*

来源：Biochemical and Biophysical Research Communications, 2010, 403(1): 59-65.

DOI：10.1016/j.bbrc.2010.10.115

• Orexin-A
• Orexin receptor
• Angiogenesis
• Vascular endothelial cells
• Extracellular signal regulated kinase 1/2 (ERK1/2)

Orexin-A, a neuropeptide originally discovered in the hypothalamus, is found in peripheral organs, as well as in the central nervous system, and is involved in the regulation of food intake, energy homeostasis, and cardiovascular functions. In this study, we report that orexin-A induces in vivo neovascularization in a mouse Matrigel plug and ex vivo sprouting of endothelial cells in rat aortic rings. We also show that orexin-A increases migration and tube formation in human umbilical vein endothelial cells (HUVECs), and this effect is mediated by orexin receptors on endothelial cells. Moreover, orexin-A activates the extracellular signal-regulated kinase 1/2 (ERK1/2) in HUVECs, which is closely linked to angiogenic responses. The inhibition of ERK activation significantly suppresses orexin-A-stimulated endothelial angiogenesis. Taken together, our results indicate that orexin-A functions as a new proangiogenic peptide and requires MEK/ERK-dependent pathway for its angiogenic actions. These results suggest orexin-A and its receptor may act as important modulators of angiogenesis under pathophysiological conditions.

• 出版日期2010-12-3