Document Detail


Leukotriene receptor antagonism and the prevention of extracellular matrix degradation during atherosclerosis and in-stent stenosis.
MedLine Citation:
PMID:  19164806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hanna Hlawaty; Marie-Paule Jacob; Liliane Louedec; Didier Letourneur; Charles Brink; Jean-Baptiste Michel; Laurent Feldman; Magnus Bäck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-22
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  29     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2009 Apr 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  518-24     Citation Subset:  IM    
Affiliation:
INSERM U698, University of Paris, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Amidines / administration & dosage,  pharmacology*
Angioplasty, Balloon* / adverse effects,  instrumentation
Animals
Carbamates / administration & dosage,  pharmacology*
Carotid Artery, Common / drug effects*,  metabolism,  pathology
Carotid Stenosis / etiology,  metabolism,  pathology,  therapy*
Cell Line
Cell Movement / drug effects
Cell Proliferation / drug effects
Cholesterol, Dietary / administration & dosage
Disease Models, Animal
Extracellular Matrix / metabolism*
Humans
Hyperplasia
Leukotriene Antagonists / administration & dosage,  pharmacology*
Leukotriene B4 / metabolism*
Macrophages / drug effects,  metabolism
Male
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 Interference
RNA, Small Interfering / metabolism
Rabbits
Recurrence / prevention & control
Stents*
Time Factors
Transfection
Chemical
Reg. No./Substance:
0/Amidines; 0/Carbamates; 0/Cholesterol, Dietary; 0/Leukotriene Antagonists; 0/RNA, Small Interfering; 0/amelubant; 71160-24-2/Leukotriene B4; 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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