| Flow shear stress and atherosclerosis: a matter of site specificity. | |
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MedLine Citation:
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PMID: 21050140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is well accepted that atherosclerosis occurs in a site-specific manner especially at branch points where disturbed blood flow (d-flow) predisposes to the development of plaques. Investigations both in vivo and in vitro have shown that d-flow is pro-atherogenic by promoting oxidative and inflammatory states in the artery wall. In contrast, steady laminar blood flow (s-flow) is atheroprotective by inhibition of oxidative stress and inflammation in the vessel wall. The mechanism for inflammation in endothelial cells (ECs) exposed to d-flow has been well studied and includes redox-dependent activation of apoptosis signal-regulating kinase 1 (ASK1) and Jun NH2-terminal kinase (JNK) that ultimately lead to the expression of adhesive molecules. In contrast, s-flow leads to the activation of the mitogen extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) pathway that prevents pro-inflammatory signaling. Important transcriptional events that reflect the pro-oxidant and pro-inflammatory condition of ECs in d-flow include the activation of activator protein 1 (AP-1) and nuclear factor kappaB (NFκB), whereas in s-flow, activation of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2) are dominant. Recent studies have shown that protein kinase c zeta (PKCζ) is highly activated under d-flow conditions and may represent a molecular switch for EC signaling and gene expression. The targeted modulation of proteins activated in a site-specific manner holds the promise for a new approach to limit atherosclerosis. |
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Authors:
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Patrizia Nigro; Jun-Ichi Abe; Bradford C Berk |
Publication Detail:
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Type: Journal Article; Review Date: 2011-04-08 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 15 ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-07-28 Completed Date: 2011-11-22 Revised Date: 2012-05-04 |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 1405-14 Citation Subset: IM |
Affiliation:
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Department of Medicine, Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / genetics, metabolism* Endothelial Cells / metabolism Gene Expression Regulation Hemodynamics / physiology* Humans Phenotype Protein Kinase C / metabolism Reactive Oxygen Species / metabolism Shear Strength Signal Transduction / physiology Stress, Mechanical* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL064839-10/HL/NHLBI NIH HHS; R01 HL064839-11/HL/NHLBI NIH HHS; R01 HL102746/HL/NHLBI NIH HHS; R01 HL108551-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; EC 2.7.11.1/protein kinase C zeta; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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