| High Fat Diet Increases and the Polyphenol, S17834, Decreases Acetylation of the SirT1-Dependent Lysine-382 on p53 and Apoptotic Signaling in Atherosclerotic Lesion-Prone Aortic Endothelium of Normal Mice. | |
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MedLine Citation:
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PMID: 21654327 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Our purpose was to determine if high fat diet and treatment with a polyphenol regulates acetylation of lysine-382 of p53, the site regulated by sirtuin-1, and apoptosis in the endothelium of the atherosclerotic lesion-prone mouse aortic arch. In cultured endothelial cells two atherogenic stimuli, hydrogen peroxide and tumor necrosis factor-α, increased acetylation of p53 lysine-382, as well as caspase-3 cleavage, an indicator of apoptotic signaling. The polyphenol, S17834, significantly prevented these changes. In LDL receptor-deficient mice, a high fat diet increased, and treatment with S17834 attenuated early atherosclerotic lesions on the lesser curvature of the aortic arch. In wild type C57BL6 mice fed the same diet, no atherosclerotic lesions were observed in this lesion-prone area, but p53 acetylation and caspase-3 cleavage increased in the endothelium. In high fat fed mice, S17834 increased sirtuin-1 protein in the lesion-prone endothelium and prevented both the increase in p53 acetylation and caspase-3 cleavage without affecting blood lipids. These results indicate that high fat diet increases and S17834 decreases acetylation of p53 in lesion-prone aortic endothelial cells of normal mice independently of blood lipids, suggesting that the polyphenol may regulate endothelial cell p53 acetylation and apoptosis via local actions. |
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Authors:
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Shanqin Xu; Bingbing Jiang; Xiuyun Hou; Chaomei Shi; Markus Bachschmid; Mengwei Zang; Tony J Verbeuren; Richard A Cohen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-03 |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: - ISSN: 1533-4023 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts (S.X., B.J., X.H., C.S., M.B., M.Z., R.A.C.) and Institut de Recherche Servier, Suresnes, France (T.J.V.). |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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