Document Detail


Aspirin inhibits MMP-2 and MMP-9 expressions and activities through upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDL-stimulated macrophages derived from human monocytes.
MedLine Citation:
PMID:  18971601     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, aspirin has been shown to alleviate matrix metalloproteinase (MMP) expression, but the underlying mechanism is still unclear. In this study, the effects of aspirin on oxidative low-density lipoprotein (ox-LDL)-stimulated human monocyte-derived macrophages were examined. Following treatment of cells with aspirin, MMP-2 and MMP-9 expression and release were significantly reduced. Moreover, expression of peroxisome proliferator-activated receptors (PPARs) alpha and gamma was markedly enhanced. The effect of PPAR inhibitors on MMP levels in aspirin-treated cells was examined. RT-PCR and ELISA assays showed that inhibition of MMP-9 levels by aspirin was notably alleviated by PPAR antagonists. Interestingly, expression of nuclear factor (NF)- kappaB was also decreased by aspirin. RT-PCR study also indicated that aspirin could upregulate the expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. In all of these studies, lower dosage (50 or 100 microg/ml) exerted the best effect. These results demonstrate that aspirin could inhibit MMP-2 and MMP-9 expression through upregulation of PPARalpha/gamma expression in ox-LDL-stimulated macrophages, and could potentially inhibit MMP-2 and MMP-9 activity by induction of TIMP-1 and TIMP-2 expression. This finding may demonstrate a novel pharmacological effect of aspirin protecting against atherosclerotic plaque rupture.
Authors:
Yinan Hua; Jie Xue; Fan Sun; Lujia Zhu; Meilin Xie
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-30
Journal Detail:
Title:  Pharmacology     Volume:  83     ISSN:  1423-0313     ISO Abbreviation:  Pharmacology     Publication Date:  2009  
Date Detail:
Created Date:  2008-12-18     Completed Date:  2009-02-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  18-25     Citation Subset:  IM    
Affiliation:
Department of Pharmacology in Medical College, Soochow University, Suzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Aspirin / administration & dosage,  pharmacology*
Cell Line
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Humans
Lipoproteins, LDL / drug effects*,  metabolism
Macrophages / drug effects,  metabolism*
Matrix Metalloproteinase 2 / drug effects,  metabolism
Matrix Metalloproteinase 9 / drug effects,  metabolism
Monocytes / drug effects,  metabolism
PPAR alpha / drug effects,  metabolism
PPAR gamma / drug effects,  metabolism
Platelet Aggregation Inhibitors / administration & dosage,  pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-1 / drug effects,  metabolism
Tissue Inhibitor of Metalloproteinase-2 / drug effects,  metabolism
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Lipoproteins, LDL; 0/PPAR alpha; 0/PPAR gamma; 0/Platelet Aggregation Inhibitors; 0/Tissue Inhibitor of Metalloproteinase-1; 0/oxidized low density lipoprotein; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 50-78-2/Aspirin; 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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