Effects of rosiglitazone on the expression of nuclear factor-κB P65 and metalloproteinase-9 mRNA in peripheral blood monocyte-derived macrophages in patients with coronary artery disease

Objective To investigate the effects and mechanisms of rosiglitazone on the expressions of nuclear factor-κB and matrix metalloprotease (MMP-9) in peripheral blood monocyte-derived macrophages (MDMs) in patients with coronary heart disease. Method This was a clinical case-control study. Forty-eight actue coronary symdrome (ACS) patients (ACS group), and 20 patients with stable angina (SA) (control group) were collected. They were performed coronary arteriography in the Department of Cardiology of the Second Xiangya Hospital from March to April in 2007. Exclusion criteria included acute infection, trauma or surgery patients within four weeks, cerebral vascular accident, liver and kidney dysfunction, cancer, and so on. The peripheral blood mononuclear cells were isolated and transformed into MDMs with macrophage colony-stimulating factor treatment. The transformed MDMs were randomly assigned into subgrougs and incubated with 0 /μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L of rosiglitazone respectively. The expressions of PPAR-γ mRNA, MMP-9 mRNA were determined by RT-PCR and nuclear factor-κB P65 (NF-KB P65) expression by immunohistochemistry. Multiple comparisons were examined for significant differences using analysis of variance (ANOVA). Results The basal expression of PPAR-y mRNA was lower, in contrast, the levels of NF-KB P65 and MMP-9 mRNA were higher in ACS group than control group. PPAR-γ mRNA expression were significantly upregulated in both ACS and control groups with rosiglitazone treatment. PPAR-γ mRNA expression was positive correlation, while the expressions of MMP-9 mRNA were negative correlation with the rosiglitazone concentration in the ACS group. Rosiglitazone inhibited the expression of NF-KB in a concentration-independent manner in ACS and control groups. Conclusions The expression of PPAR-y mRNA is inhibited, while the activity of NF-KB and expression of MMP-9 mRNA are enhanced in MDMs of ACS cases. Rosiglitazone intervention may inhibit NF-KB activity and MMP-9 expression by upregulation of PPAR-y expression in MDMS of patiens with ACS.     

罗格列酮对冠心病患者巨噬细胞表达核因子-κB和金属蛋白酶-9的影响

目的 探讨罗格列酮(Ros)干预在调节冠心病患者外周血单核细胞源性巨噬细胞(MDMs)表达核因子-κB(NF-κB)、金属蛋白酶-9(MMP-19)中的作用及可能机制.方法 本研究为临床病例对照研究.于2007年3月至4月间,从湘雅二医院心内科行冠脉造影患者中,选取急性冠脉综合征患者48例(ACS组)、稳定型心绞痛(SA)患者20例(对照组)为研究对象,排除脑血管意外、急性感染和创伤、肝肾功能不全、肿瘤等患者.提取外周血单个核细胞,用巨噬细胞集落刺激因子刺激,转化为MDMs;随机分亚组后,分别用0μmol/L1μmol/L,10 μmol/L,20 μmol浓度Ros干预48h;RT-PCR检测各亚组MDMs表达过氧化物酶增殖体激活受体-γ([PPAR-γ)和MMP-9 mRNA,免疫组化法检测NF-κB P65表达强度.用ANOVA检验比较组间及亚组内MDMs在表达PPAR-γ,MMP-9,NF-κB P65的差异.结果 干预前,ACS组MDMs表达PPAR-γmRNA水平低于对照组,表达NF-κB P65及MMP-9mRNA水平高于对照组;Ros干预后,ACS组及对照组PPAR-γmRNA表达明显上调,ACS组PPAR-γ的表达量与Ros浓度呈正变关系;MMP-9 mRNA表达下调,在ACs组其下调程度与Ros浓度呈反变关系;两组NF-κB P65表达量均呈现非剂量依赖性降低.结论 ACS患者外周血MDMs的PPAR-γRNA表达被抑制、NF-γB活性及MMP-9 mRNA表达增强.Ros干预可通过增加PPAR-γ的表达,从而抑制NF-κB活性和MMP-9的表达.