Effects of PPAR-γ agonist rosiglitazone on MMP-9 and TIMP-1 expression of monocyte-derived macrophages isolated from patients with acute coronary syndrome
10.3760/cma.j.issn.0253-3758.2009.08.016
- VernacularTitle:过氧化物酶增殖物激活受体-γ调节体外诱导培养的人巨噬细胞表达基质金属蛋白酶-9及其抑制物-1的作用及机制
- Author:
Yu-Mei LUO
1
;
Xin-Hong WAN
;
De-Qian JIANG
;
Wen-Yong KUANG
;
Hong-Bo GUO
;
Zhao-Xia CHEN
;
He-Jin WANG
;
Li-Hua XIE
;
Wen DUAN
Author Information
1. 广东省深圳市龙岗区人民医院
- Keywords:
Coronary disease;
Macrophages;
Peroxisome proliferator-activated receptors;
NF-kappaB;
Matrix metalloproteinase 9
- From:
Chinese Journal of Cardiology
2009;37(8):739-745
- CountryChina
- Language:Chinese
-
Abstract:
Objective 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 peroxisotne proliferator-activated receptor-γ (PPAR-γ) is involved in a variety of inflammatory cytokine gene transcriptional regulations. We explored the possible role of PPAR-γ in the regulation of MMP-9 and TIMP-1 expressed by peripheral monocyte-derived macrophages (MDMs) from patients with ACS. Methods Peripheral blood mononuclear cells were isolated from 48 patients with ACS and 28 healthy controls and stimulated by macrophage colony-stimulating factor (0. 1 μg/ml for 24 hours) to form MDMs. MDMs were then incubated under various concentrations of rosiglitazone (0, 1, 10, 20 μmol/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-γ, MMP-9 by RT-PCR and nuclear factor-KB P65 ( NF-kB P65 ) expression by immunohistochemistry. Results PPAR-γ mRNA expression was significantly lower while NF-kB 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-γ 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-kB P65 expression in both groups. Conclusion Rosiglitazone intervention may downregulate MMP-9 expression by upregulating PPAR-γ expression, and by downregulaiting NF-kB expression in MDMs isolated from patients with ACS.
