| Simvastatin inhibits glucose-stimulated vascular smooth muscle cell migration involving increased expression of RhoB and a block of Ras/Akt signal. | |
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MedLine Citation:
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PMID: 20946258 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Diabetic patients are at high risk to develop atherosclerotic cardiovascular disease and have a higher restenotic rate after percutaneous coronary intervention (PCI). Statins improve cardiovascular outcome and reduce restenosis after PCI by inhibiting proliferation and migration of vascular smooth muscle cells (VSMCs). But the effect of statins on diabetes without dyslipidemia was still not fully understood. Our previous study has demonstrated that simvastatin inhibits VSMC proliferation in high glucose status without dyslipidemia, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and upregulation of p53, p21, p16, and p27. METHOD: Following our previous study, we investigated the mechanism of simvastatin inhibition of VSMC migration in a diabetes-like model (A7r5 cells under high glucose conditions without dyslipidemia). RESULTS: Under high glucose conditions, simvastatin dose-dependently inhibited VSMC migration, decreased PI3K/Akt pathway activity, reduced c-Raf and Ras expression, increased RhoB but not RhoA, Rac1, and Cdc2 expression, dose-dependently inhibited MMP-2, but not MMP-9, activity, and dose-dependently inhibited NF-κB activity. CONCLUSION: The inhibition of VSMC migration under high glucose conditions was via two different pathways. The first pathway is mevalonate-related but not RhoA protein-related and involves suppression of Ras and PI3K/Akt signals. The second pathway is not mevalonate-related and involves increasing RhoB expression directly. |
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Authors:
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Kuei-Chuan Chan; Cheng-Hsun Wu; Chien-Ning Huang; Kuang-Ping Lan; Wen Chun Chang; Chau-Jong Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-14 |
Journal Detail:
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Title: Cardiovascular therapeutics Volume: 30 ISSN: 1755-5922 ISO Abbreviation: Cardiovasc Ther Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101319630 Medline TA: Cardiovasc Ther Country: England |
Other Details:
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Languages: eng Pagination: 75-84 Citation Subset: IM |
Copyright Information:
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© 2010 Blackwell Publishing Ltd. |
Affiliation:
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Department of Internal Medicine, Chung-Shan Medical University Hospital, School of Medicine, Chung-Shan Medical University, No. 110 Sector 1 Jianguo N. Road, Taichung 402, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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