Involvement of COX‐2/PGE2 signalling in hypoxia‐induced angiogenic response in endothelial cells

Journal of Cellular and Molecular Medicine

Lixing Zhao¹  Yeke Wu¹  Zhenrui Xu¹  Hui Wang²  Zhihe Zhao¹  Yu Li¹  Pu Yang¹ 

[1] State Key Laboratory of Oral Diseases, Department of Orthodontics, West China College of Stomatology, Sichuan University, Chengdu, China;State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China

关键词: hypoxia;    endothelial cells;    angiogenesis;    COX‐2/PGE2 signalling;    VEGF;    AQP1;   

DOI  :  10.1111/j.1582-4934.2011.01479.x

来源: Wiley

【 摘 要 】

Abstract

To evaluate the impact of hypoxia on the angiogenic capability of endothelial cells (ECs), and further investigate whether the cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PGE₂) signalling is involved in the angiogenic response of ECs to hypoxia. We explored the impact of various periods (1, 3, 6, 12, 24 hrs) of hypoxia (2% O₂) on human umbilical vein endothelial cells (HUVECs) in vitro. We observed cell viability, migration, tube formation, analysed COX-2, vascular endothelial growth factor (VEGF), AQP1 mRNA transcription, protein expression and measured PGE₂, VEGF protein concentration in cell supernatants. Then we treated HUVECs with COX-2 selective inhibitor NS398, EP1/2 combined antagonist AH6809 and exogenous PGE₂ to investigate the role of COX-2/PGE₂ signalling in the angiogenic response of ECs to hypoxia. The results demonstrated that short-term hypoxic treatment enhanced HUVECs proliferation, migration, tube formation, significantly up-regulated COX-2, VEGF, AQP1 mRNA level, protein expression and promoted PGE₂, VEGF release. The pharmacological inhibition study revealed that exposure of HUVEC to NS398 and AH6809 under hypoxia impaired the biological responses of ECs to hypoxia. Exogenous PGE₂ augments the effects of hypoxia on HUVECs, and partially reversed the inhibitory effects of NS398 on HUVECs proliferation and angiogenic capability. Short-term hypoxic treatment enhanced angiogenic capability of ECs, and COX-2/PGE₂ signalling may play a critical role in the biological response of ECs to hypoxia.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd