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 E(2) ( PGE(2)) 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% O(2)) 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 PGE(2), VEGF protein concentration in cell supernatants. Then we treated HUVECs with COX-2 selective inhibitor NS398, EP1/2 combined antagonist AH6809 and exogenous PGE(2) to investigate the role of COX-2/ PGE(2) 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 PGE(2) , 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 PGE(2) 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/ PGE(2) signalling may play a critical role in the biological response of ECs to hypoxia.
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Authors | Lixing Zhao, Yeke Wu, Zhenrui Xu, Hui Wang, Zhihe Zhao, Yu Li, Pu Yang, Xing Wei |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
Vol. 16
Issue 8
Pg. 1840-55
(Aug 2012)
ISSN: 1582-4934 [Electronic] England |
PMID | 22050691
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
Chemical References |
- Cyclooxygenase 2 Inhibitors
- Nitrobenzenes
- RNA, Messenger
- Receptors, Prostaglandin E, EP1 Subtype
- Receptors, Prostaglandin E, EP2 Subtype
- Sulfonamides
- Vascular Endothelial Growth Factor A
- Xanthones
- N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
- Aquaporin 1
- 6-isopropoxy-9-oxoxanthene-2-carboxylic acid
- Cyclooxygenase 2
- PTGS2 protein, human
- Dinoprostone
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Topics |
- Aquaporin 1
(genetics, metabolism)
- Cell Hypoxia
(drug effects)
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Shape
(drug effects)
- Cell Survival
(drug effects)
- Cyclooxygenase 2
(genetics, metabolism)
- Cyclooxygenase 2 Inhibitors
(pharmacology)
- Dinoprostone
(metabolism)
- Gene Expression Regulation
(drug effects)
- Human Umbilical Vein Endothelial Cells
(cytology, drug effects, enzymology)
- Humans
- Immunohistochemistry
- Neovascularization, Physiologic
(drug effects, genetics)
- Nitrobenzenes
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Receptors, Prostaglandin E, EP1 Subtype
(metabolism)
- Receptors, Prostaglandin E, EP2 Subtype
(metabolism)
- Signal Transduction
(drug effects)
- Sulfonamides
(pharmacology)
- Time Factors
- Transcription, Genetic
(drug effects)
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- Xanthones
(pharmacology)
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