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学科主题: 基础医学
题名:
Microsomal Prostaglandin E Synthase-1-Derived PGE(2) Inhibits Vascular Smooth Muscle Cell Calcification
作者: Gao, Cheng1,3; Fu, Yi1,3; Li, Yanhui2,3; Zhang, Xu1,3; Zhang, Lu1,3; Yu, Fang1,3; Xu, Susanna S.4; Xu, Qingbo5; Zhu, Yi1,3; Guan, Youfei1,3; Wang, Xian1,3; Kong, Wei1,3
关键词: adenine ; calcium ; myocardial infarction ; phosphates ; vascular calcification
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2016
DOI: 10.1161/ATVBAHA.115.306642
卷: 36, 期:1, 页:108-121
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: UP-REGULATION ; CARDIOVASCULAR BIOLOGY ; BONE-RESORPTION ; E-2 ; CYCLOOXYGENASE-2 ; MICE ; PROSTACYCLIN ; RECEPTOR ; DISEASE ; MECHANISMS
英文摘要:

Objective Chronic administration of selective cyclooxygenase-2 (COX-2) inhibitors leads to an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. Vascular smooth muscle cell (VSMC) calcification, a common complication of chronic kidney disease, is directly related to cardiovascular morbidity and mortality. Here, we tested whether specific COX-2 inhibition affects vascular calcification during chronic renal failure.

Approach and Results The COX-2-specific inhibitors NS398 and SC236 significantly increased high-phosphate (Pi)-induced VSMC calcification. Similarly, COX-2(-/-) VSMCs, COX-2(-/-) aortas rings treated with high Pi and adenine diet-induced COX-2(-/-) chronic renal failure mice displayed enhanced calcium deposition. Metabolomic analysis revealed the differential suppression of PGE(2) production by COX-1- and COX-2-specific inhibitors in high-Pi-stimulated VSMCs, indicating the involvement of PGE(2) during COX-2 inhibition-aggravated vascular calcification. Indeed, exogenous PGE(2) reduced alkaline phosphatase activity, osteogenic transdifferentiation, apoptosis, and calcification of VSMCs. In accordance, downregulation of microsomal prostaglandin E synthase (mPGES)-1 in VSMCs, mPGES-1(-/-) aorta with high-Pi stimulation and mPGES-1(-/-) chronic renal failure mice resulted in enhanced vascular mineralization. Further applications of RNAi and specific antagonists for PGE(2) receptors indicated EP4 may mediate PGE(2)-inhibited vascular calcification.

Conclusions Our data revealed the pivotal role of COX-2-mPGES-1-PGE(2) axis in vascular calcification. The selective inhibition of COX-2 or mPGES-1 may increase the risk of calcification and subsequent adverse cardiovascular events during chronic renal failure.

语种: 英语
所属项目编号: 2012CB518002 ; 2011CB503904 ; 91539203 ; 81121061 ; 81225002 ; 81220108004 ; B07001
项目资助者: National Program on Key Basic Research Projects (973 Program) ; National Natural Science Foundation of the P.R. China ; National Science Fund for distinguished Young Scholars ; International Cooperation and Exchanges National Natural Science Foundation of the P.R. China ; 111 Project of Chinese Ministry of Education
WOS记录号: WOS:000367000000015
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68044
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Univ Cambridge, Gonville & Caius Coll, Cambridge, England
3.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
5.Kings Coll London, BHF Ctr, Div Cardiovasc, London WC2R 2LS, England

Recommended Citation:
Gao, Cheng,Fu, Yi,Li, Yanhui,et al. Microsomal Prostaglandin E Synthase-1-Derived PGE(2) Inhibits Vascular Smooth Muscle Cell Calcification[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2016,36(1):108-121.
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