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.

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Hua Y, Xue J, Sun F, Zhu L, Xie M

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.

Pharmacology. 2009;83(1):18-25. doi: 10.1159/000166183. Epub 2008 Oct 30.

PubMed ID

18971601 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
72 kDa type IV collagenase	P08253	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Acetylsalicylic acid	Approved Vet Approved	TIMP1	7076	upregulated	Aspirin results in increased expression of TIMP1 mRNA	Xp11.3
Acetylsalicylic acid	Approved Vet Approved	TIMP2	7077	upregulated	Aspirin results in increased expression of TIMP2 mRNA	17q25.3