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Effects of PPAR-gamma agonist rosiglitazone on MMP-9 and TIMP-1 expression of monocyte-derived macrophages isolated from patients with acute coronary syndrome / 中华心血管病杂志
Chinese Journal of Cardiology ; (12): 739-745, 2009.
Article Dans Chinois | WPRIM | ID: wpr-236414
ABSTRACT
<p><b>OBJECTIVE</b>Coronary arterial plaque rupture and secondary thrombosis are the major pathogenesis of acute coronary syndrome (ACS). Metalloprotease (MMPs) secreted by monocyte/macrophage was the main predisposing factor of the plaque rupture and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is involved in a variety of inflammatory cytokine gene transcriptional regulations. We explored the possible role of PPAR-gamma in the regulation of MMP-9 and TIMP-1 expressed by peripheral monocyte-derived macrophages (MDMs) from patients with ACS.</p><p><b>METHODS</b>Peripheral blood mononuclear cells were isolated from 48 patients with ACS and 28 healthy controls and stimulated by macrophage colony-stimulating factor (0.1 microg/ml for 24 hours) to form MDMs. MDMs were then incubated under various concentrations of rosiglitazone (0, 1, 10, 20 micromol/L) for 48 hours. The concentrations of MMP-9 and TIMP-1 in the supernatant were measured by enzyme linked immunosorbent assay, and the mRNA expression of PPAR-gamma, MMP-9 by RT-PCR and nuclear factor-kappaB P65 (NF-kappaB P65) expression by immunohistochemistry.</p><p><b>RESULTS</b>PPAR-gamma mRNA expression was significantly lower while NF-kappaB P65 and MMP-9 expression as well as MMP-9 and TIMP-1 concentrations in supernatant were significantly higher in ACS group than those in control group (all P < 0.05). After rosiglitazone intervention, PPAR-gamma mRNA expression was significantly upregulated in both ACS and control groups in a dose-dependent manner. Both the MMP-9 concentration in the supernatant and MMP-9 mRNA expression were reduced post intervention with rosiglitazone in both groups. The TIMP-1 mRNA expression and concentration in supernatant were not affected by rosiglitazone in both groups. Rosiglitazone induced significant downregulation of NF-kappaB P65 expression in both groups.</p><p><b>CONCLUSION</b>Rosiglitazone intervention may downregulate MMP-9 expression by upregulating PPAR-gamma expression, and by downregulating NF-kappaB expression in MDMs isolated from patients with ACS.</p>
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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Vasodilatateurs / Sang / Études cas-témoins / Cellules cultivées / Inhibiteur tissulaire de métalloprotéinase-1 / Matrix metalloproteinase 9 / Thiazolidinediones / Récepteur PPAR gamma / Facteur de transcription RelA Type d'étude: Étude observationnelle Limites du sujet: Adulte très âgé / Femelle / Humains / Mâle langue: Chinois Texte intégral: Chinese Journal of Cardiology Année: 2009 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Vasodilatateurs / Sang / Études cas-témoins / Cellules cultivées / Inhibiteur tissulaire de métalloprotéinase-1 / Matrix metalloproteinase 9 / Thiazolidinediones / Récepteur PPAR gamma / Facteur de transcription RelA Type d'étude: Étude observationnelle Limites du sujet: Adulte très âgé / Femelle / Humains / Mâle langue: Chinois Texte intégral: Chinese Journal of Cardiology Année: 2009 Type: Article