| Acetylbritannilactone induces G(1) arrest and apoptosis in vascular smooth muscle cells. | |
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MedLine Citation:
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PMID: 20060605 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: The present study was designed to determine the effects of Acetylbritannilactone (ABL), a naturally occurring Inula britannica L., on vascular smooth muscle cell (VSMC) proliferation and apoptosis. METHODS: In vitro experiments were performed to evaluate the effects of ABL on the VSMC cycle and apoptosis stimulated by chemoattractant. In addition, to examine the effects of ABL in vivo, balloon injury to rat carotid arteries was performed. RESULTS: ABL treatment inhibited platelet-derived growth factor (PDGF) induced DNA synthesis and proliferation in cultured VSMC. Such growth-inhibitory effects of ABL were associated with G(1) phase arrest, which were correlated with reduction of cyclins D1, A, and E expression and cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 proteins, increased the CDK inhibitory protein p21(cip1) expression, and enhanced the binding of p21(cip1) to CDKs. In addition, ABL also induced apoptosis in proliferative VSMCs, as evidenced by the induction of a higher ratio of Bax/Bcl-2, activation of caspase-9, caspase-3, and the cleavage of endogenous substrate Poly (ADP-ribose) polymerase. However, pretreatment with pan-caspases inhibitor (z-VAD-fmk) only partially reversed ABL-induced apoptosis, suggesting the involvement of both caspase-dependent and caspase-independent pathways in these processes. Furthermore, the effects of ABL on VSMCs were associated with the downregulation of extracellular signal-regulated kinase (ERK) 1/2 signaling pathways. In vivo, ABL (26mg/kg/day) significantly suppressed injury-induced ERK1/2 phosphorylation, and increased VSMC apoptosis 14days after balloon injury. CONCLUSIONS: Our findings demonstrated that ABL was capable of suppressing the abnormal VSMC proliferation, accompanied by the induction of apoptosis in vivo and in vitro. It suggested that ABL could be considered a pharmacological candidate for the prevention of restenosis after balloon angioplasty. |
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Authors:
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Bin Liu; Mei Han; Rong-Hua Sun; Jun-Jie Wang; Yue-Ping Liu; Jin-Kun Wen |
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Publication Detail:
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Type: Journal Article Date: 2010-01-08 |
Journal Detail:
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Title: International journal of cardiology Volume: 149 ISSN: 1874-1754 ISO Abbreviation: Int. J. Cardiol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 30-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2009 Elsevier Ireland Ltd. All rights reserved. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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