Academic Journal
Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice
| العنوان: | Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice |
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| المؤلفون: | Dai, Xiao-Yan, Cai, Yan, Mao, Ding-Ding, Qi, Yong-Fen, Tang, Chaoshu, Xu, Qingbo, Zhu, Yi, Xu, Ming-Jiang, Wang, Xian |
| المساهمون: | Xu, MJ (reprint author), Peking Univ, Key Lab Mol Cardiovasc Sci, Sch Basic Med Sci, Hlth Sci Ctr,Dept Physiol & Pathophysiol,Minist E, Beijing 100191, Peoples R China., Peking Univ, Key Lab Mol Cardiovasc Sci, Sch Basic Med Sci, Hlth Sci Ctr,Dept Physiol & Pathophysiol,Minist E, Beijing 100191, Peoples R China., Kings Coll London, British Heart Fdn Ctr, Div Cardiovasc, London WC2R 2LS, England. |
| المصدر: | PubMed ; SCI |
| بيانات النشر: | journal of molecular and cellular cardiology |
| سنة النشر: | 2012 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | Atherosclerosis, Macrophage, Peptide, Scavenger receptor, FOAM CELL-FORMATION, LOW-DENSITY-LIPOPROTEIN, SR-A EXPRESSION, LIPID UPTAKE, HYPERLIPIDEMIC MICE, ALZHEIMERS-DISEASE, TUMOR-SUPPRESSOR, TRANSGENIC MICE, PROTEIN, PTEN |
| الوصف: | 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. ; Cardiac & Cardiovascular Systems ; Cell Biology ; SCI(E) ; PubMed ; 5 ; ARTICLE ; 4 ; 509-520 ; 53 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-2828 1095-8584 |
| Relation: | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY.2012,53,(4),509-520.; 659078; http://hdl.handle.net/20.500.11897/191485; WOS:000308679700006 |
| DOI: | 10.1016/j.yjmcc.2012.07.006 |
| الاتاحة: | https://hdl.handle.net/20.500.11897/191485 https://doi.org/10.1016/j.yjmcc.2012.07.006 |
| رقم الانضمام: | edsbas.B6AA0217 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222828 10958584 |
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| DOI: | 10.1016/j.yjmcc.2012.07.006 |