IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice
Dai, Xiao-Yan; Cai, Yan; Mao, Ding-Ding; Qi, Yong-Fen; Tang, Chaoshu; Xu, Qingbo2; Zhu, Yi; Xu, Ming-Jiang1; Wang, Xian
关键词Atherosclerosis Macrophage Peptide Scavenger receptor
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2012-10-01
DOI10.1016/j.yjmcc.2012.07.006
53期:4页:509-520
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Cell Biology
资助者Major National Basic Research Program of China ; National Natural Science Foundation of China ; "111" Project of the Ministry of Education of China ; Major National Basic Research Program of China ; National Natural Science Foundation of China ; "111" Project of the Ministry of Education of China
研究领域[WOS]Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]FOAM CELL-FORMATION ; LOW-DENSITY-LIPOPROTEIN ; SR-A EXPRESSION ; LIPID UPTAKE ; HYPERLIPIDEMIC MICE ; ALZHEIMERS-DISEASE ; TUMOR-SUPPRESSOR ; TRANSGENIC MICE ; PROTEIN ; PTEN
英文摘要

Intermedin, a novel member of calcitonin gene-related peptide family, is an endogenous cardiovascular-protective peptide. Because intermedin exists in human atherosclerotic plaque, we studied the role of intermedin in macrophage scavenger receptor A (SR-A)-mediated foam-cell formation and atherogenesis. In an in vitro foam-cell formation model (induced by acetylated low-density lipoprotein [AcLDL]) with mouse (C57BL/6J) macrophages, intermedin reduced AcLDL uptake and binding, decreased intracellular cholesterol content, and suppressed both mRNA and protein levels of SR-A. Simultaneously, intermedin increased phosphatase and tensin homolog (PTEN) protein levels by increasing PTEN phosphorylation and inhibiting ubiquitin-mediated PTEN degradation. These effects were blocked by the intermedin receptor antagonist or cAMP-protein kinase A inhibitors. PTEN overexpression mimicked the inhibitory effects of intermedin on SR-A expression and AcLDL uptake. However, knockdown of PTEN by short-hairpin RNA completely blocked all inhibitory effects of intermedin. Furthermore, in apolipoprotein E-deficient (apoE(-/-)) mice, 6-week intermedin infusion reduced AcLDL uptake and SR-A mRNA and protein levels and increased PTEN protein level in peritoneal macrophages. PTEN level was increased and SR-A expression decreased in parallel in macrophages in atherosclerotic lesions. Thus, intermedin inhibited atherosclerosis in apoE(-/-) mice. Increased stability of FTEN by intermedin leads to SR-A inhibition in macrophages, which ameliorates foam-cell formation and atherosclerosis in apoE(-/-) mice. (c) 2012 Elsevier Ltd. All rights reserved.

语种英语
所属项目编号2012CB518002 ; 2011CB503904 ; 81121061 ; 81070683 ; 30900566 ; 81170099 ; B07001
资助者Major National Basic Research Program of China ; National Natural Science Foundation of China ; "111" Project of the Ministry of Education of China ; Major National Basic Research Program of China ; National Natural Science Foundation of China ; "111" Project of the Ministry of Education of China
WOS记录号WOS:000308679700006
Citation statistics
Cited Times:20[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63538
Collection北京大学基础医学院_心血管所
作者单位1.Peking Univ, Key Lab Mol Cardiovasc Sci, Sch Basic Med Sci, Hlth Sci Ctr,Dept Physiol & Pathophysiol,Minist E, Beijing 100191, Peoples R China
2.Kings Coll London, British Heart Fdn Ctr, Div Cardiovasc, London WC2R 2LS, England
Recommended Citation
GB/T 7714
Dai, Xiao-Yan,Cai, Yan,Mao, Ding-Ding,et al. Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2012,53(4):509-520.
APA Dai, Xiao-Yan.,Cai, Yan.,Mao, Ding-Ding.,Qi, Yong-Fen.,Tang, Chaoshu.,...&Wang, Xian.(2012).Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,53(4),509-520.
MLA Dai, Xiao-Yan,et al."Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 53.4(2012):509-520.
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