| Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection. | |
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MedLine Citation:
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PMID: 19040207 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Small interfering RNA (siRNA) delivery is a promising approach for the treatment of cardiovascular diseases. Matrix metalloproteinase (MMP) 2 over-expression in the arterial wall has been implicated in restenosis after percutaneous coronary intervention, as well as in spontaneous atherosclerotic plaque rupture. We hypothesized that in vivo local delivery of siRNA targeted at MMP2 (MMP2-siRNA) in the balloon-injured carotid artery of hypercholesterolemic rabbits may lead to inhibition of MMP2 expression. METHODS: Two weeks after balloon injury, 5 micromol/l of Tamra-tagged MMP2-siRNA, scramble siRNA or saline was locally injected in the carotid artery and incubated for 1 h. RESULTS: Fluorescent microscopy studies showed the circumferential uptake of siRNA in the superficial layers of neointimal cells. MMP2 mRNA levels, measured by the real-time reverse transcriptase-polymerase chain reaction, was decreased by 79 +/- 25% in MMP2-siRNA- versus scramble siRNA-transfected arteries (p < 0.05). MMP2 activity, measured by gelatin zymography performed on the conditioned media of MMP2-siRNA versus scramble siRNA transfected arteries, decreased by 53 +/- 29%, 50 +/- 24% and 46 +/- 14% at 24, 48 and 72 h, respectively (p < 0.005 for all). No effect was observed on MMP9, pro-MMP9 and TIMP-2 levels. CONCLUSIONS: The results obtained in the present study suggest that significant inhibition of gene expression can be achieved with local delivery of siRNA in the arterial wall in vivo. |
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Authors:
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Hanna Hlawaty; Aurélie San Juan; Marie-Paule Jacob; Roger Vranckx; Didier Letourneur; Laurent J Feldman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of gene medicine Volume: 11 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-05 Completed Date: 2009-02-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
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Languages: eng Pagination: 92-9 Citation Subset: IM |
Copyright Information:
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(c) 2008 John Wiley & Sons, Ltd. |
Affiliation:
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INSERM U698, Bioingénierie Cardiovasculaire, CHU Bichat Université Paris 13, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angioplasty, Balloon
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adverse effects Animals Carotid Arteries / enzymology*, pathology* Carotid Artery Injuries / genetics, therapy* Disease Models, Animal Immunohistochemistry Male Matrix Metalloproteinase 2 / antagonists & inhibitors*, genetics, metabolism Matrix Metalloproteinase 9 / genetics, metabolism RNA Interference* RNA, Messenger / metabolism RNA, Small Interfering / administration & dosage*, metabolism Rabbits Tissue Inhibitor of Metalloproteinase-2 / genetics, metabolism Transfection |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/RNA, Small Interfering; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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