| Novel gene silencer pyrrole-imidazole polyamide targeting lectin-like oxidized low-density lipoprotein receptor-1 attenuates restenosis of the artery after injury. | |
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MedLine Citation:
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PMID: 18519843 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can support the binding, internalization, and proteolytic degradation of oxidized low-density lipoprotein. The LOX-1 expression increases in the neointima after balloon injury. To develop an efficient compound to inhibit LOX-1, we designed and synthesized a novel gene silencer pyrrole-imidazole (PI) polyamide targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) to the activator protein-1 binding site. We examined the effects of PI polyamide to LOX-1 on the LOX-1 promoter activity, the expression of LOX-1 mRNA and protein, and neointimal hyperplasia of the rat carotid artery after balloon injury. PI polyamide to LOX-1 significantly inhibited the rat LOX-1 promoter activity and decreased the expression of LOX-1 mRNA and protein. After balloon injury of the arteries, PI polyamide to LOX-1 was incubated for 10 minutes. Fluorescein isothiocyanate-labeled PI polyamide was distributed to almost all of the nuclei in the injured artery. PI polyamide to LOX-1 (100 microg) significantly inhibited the neointimal thickening by 58%. PI polyamide preserved the re-endothelialization in the injured artery. PI polyamide significantly inhibited the expression of LOX-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9 mRNAs in the injured artery. The synthetic PI polyamide to LOX-1 decreased the expression of LOX-1 and inhibited neointimal hyperplasia after arterial injury. This novel gene silencer PI polyamide to LOX-1 is, therefore, considered to be a feasible agent for the treatment of in-stent restenosis. |
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Authors:
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En-Hui Yao; Noboru Fukuda; Takahiro Ueno; Hiroyuki Matsuda; Koichi Matsumoto; Hiroki Nagase; Yoshiaki Matsumoto; Ayako Takasaka; Kazuo Serie; Hiroshi Sugiyama; Tatsuya Sawamura |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-02 |
Journal Detail:
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Title: Hypertension Volume: 52 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-20 Completed Date: 2008-07-08 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 86-92 Citation Subset: IM |
Affiliation:
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Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173-8610, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Angioplasty, Balloon
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adverse effects Animals Carotid Arteries / drug effects, pathology, surgery Cells, Cultured Coronary Restenosis / genetics, pathology, prevention & control* Drug Design Gene Expression / drug effects* Gene Silencing / drug effects Hyperplasia / genetics, prevention & control Male Nylons / chemical synthesis, chemistry, pharmacology* Promoter Regions, Genetic / drug effects Protein Biosynthesis / drug effects Pyrroles / chemical synthesis, pharmacology*, therapeutic use RNA, Messenger / metabolism Rats Rats, Wistar Scavenger Receptors, Class E / antagonists & inhibitors*, genetics Tunica Intima / drug effects*, pathology, surgery |
| Chemical | |
Reg. No./Substance:
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0/Nylons; 0/Pyrroles; 0/RNA, Messenger; 0/Scavenger Receptors, Class E |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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