|Leukotriene receptor antagonism and the prevention of extracellular matrix degradation during atherosclerosis and in-stent stenosis.|
|PMID: 19164806 Owner: NLM Status: MEDLINE|
|OBJECTIVE: The lipid-derived inflammatory mediators leukotrienes (LTs) are produced during vascular injury. The aim of the present study was to determine the role of LT receptor signaling in the pathophysiology of in-stent stenosis. METHODS AND RESULTS: New Zealand White rabbits were fed 0.3% cholesterol and subjected to angioplasty with balloon dilatation and stent implantation in the right carotid artery. Rabbits treated for 2 weeks with the BLT receptor antagonist BIIL284 (3 mg/kg once daily by oral gavage) displayed a significantly reduced in-stent intimal hyperplasia in carotid arteries compared with vehicle-treated rabbits. In addition, BIIL284 treatment significantly reduced the extracellular matrix metalloproteinase (MMP)-2 and MMP-9 activities in stented arteries. The inhibited MMP-9 activity was correlated with decreased macrophage content in the lesions. The LTB(4)-induced migration of vascular smooth muscle cells was significantly inhibited by transfection with siRNA against MMP-2. Finally, human arteries subjected to ex vivo angioplasty and stent implantation displayed an increased in-stent intimal hyperplasia and higher MMP-2 and -9 activities in the presence of LTB(4). CONCLUSIONS: These results suggest a key role of LT signaling in the extracellular matrix degradation associated with hyperlipidemia and in-stent stenosis. In conclusion, targeting LT receptors may represent a therapeutic strategy in atherosclerosis and interventional cardiology.|
|Hanna Hlawaty; Marie-Paule Jacob; Liliane Louedec; Didier Letourneur; Charles Brink; Jean-Baptiste Michel; Laurent Feldman; Magnus Bäck|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-22|
|Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Apr|
|Created Date: 2009-03-20 Completed Date: 2009-04-02 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States|
|Languages: eng Pagination: 518-24 Citation Subset: IM|
|INSERM U698, University of Paris, Paris, France.|
|APA/MLA Format Download EndNote Download BibTex|
Amidines / administration & dosage, pharmacology*
Angioplasty, Balloon* / adverse effects, instrumentation
Carbamates / administration & dosage, pharmacology*
Carotid Artery, Common / drug effects*, metabolism, pathology
Carotid Stenosis / etiology, metabolism, pathology, therapy*
Cell Movement / drug effects
Cell Proliferation / drug effects
Cholesterol, Dietary / administration & dosage
Disease Models, Animal
Extracellular Matrix / metabolism*
Leukotriene Antagonists / administration & dosage, pharmacology*
Leukotriene B4 / metabolism*
Macrophages / drug effects, metabolism
Mammary Arteries / metabolism, pathology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Muscle, Smooth, Vascular / drug effects, metabolism
Myocytes, Smooth Muscle / drug effects, metabolism
Organ Culture Techniques
RNA, Small Interfering / metabolism
Recurrence / prevention & control
|0/Amidines; 0/Carbamates; 0/Cholesterol, Dietary; 0/Leukotriene Antagonists; 0/RNA, Small Interfering; 0/amelubant; 71160-24-2/Leukotriene B4; EC 18.104.22.168/Matrix Metalloproteinase 2; EC 22.214.171.124/Matrix Metalloproteinase 9|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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