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学科主题: 基础医学
题名:
Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice
作者: 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
发表日期: 2012-10-01
DOI: 10.1016/j.yjmcc.2012.07.006
卷: 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
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
项目资助者: Major National Basic Research Program of China ; National Natural Science Foundation of China ; "111" Project of the Ministry of Education of China
WOS记录号: WOS:000308679700006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63538
Appears in Collections:基础医学院_心血管所_期刊论文

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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:
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.
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