Department of Cardiology, Medical University of Silesia, Ziołowa 47, PL 40-635 Katowice, Poland.
Pharmacol Rep. 2010 Nov-Dec;62(6):1108-16. doi: 10.1016/s1734-1140(10)70373-x.
Inflammation plays a critical role in the pathology of acute coronary syndrome (ACS). Matrix metalloproteinases (MMP)--proteolytic enzymes participating in plaque destabilization--are the crucial effectors of proinflammatory mechanisms leading to plaque rupture. Numerous reports have confirmed the significance of these factors both in circulating blood and locally in the plaque. There is, however, a lack of information on the molecular mechanisms leading to these disturbances, and the effect of standard treatment for ACS on these processes. The aim of the study was to assess the gene expression of MMP-2, -9 and TIMP-2, and the effect of standard treatment on the expression of the studied genes. The study was conducted in 32 patients with ACS and 15 healthy subjects (control group). Monocytes were isolated using Rosette-Sep kits. Gene expression of MMP-2, MMP-9 and TIMP-2 was evaluated on days 1 and 5 in the studied group and once in controls. Total mRNA was extracted from monocytes and the number of mRNA copies was assessed by QRT-PCR. Monocytes of ACS patients present with significantly higher gene expression of MMP-2, -9 and TIMP-2 compared to healthy controls (0.0915 ± 0.037 vs. 0.001 ± 0.0002, p < 0.01; 0.81 ± 0.279 vs. 0.10 ± 0.057, p < 0.05; 0.84 ± 0.140 vs. 0.42 ± 0.126, p < 0.05, respectively). After the 5-day standard treatment, a significant decrease in MMP-2 gene expression was observed. Other studied genes did not show relevant changes during the observation period. No significant correlation was found between classical atherosclerosis risk factors and the expression of the studied genes. Monocytes of ACS patients significantly overexpressed MMP-2, MMP-9 and TIMP-2. Five days of standard treatment resulted in downregulation of the MMP-2 gene. MMP gene overexpression appears to be an independent factor concerning the pathogenesis of ACS.
炎症在急性冠状动脉综合征（ACS）的病理学中起着关键作用。基质金属蛋白酶（MMP）——参与斑块不稳定的蛋白水解酶——是导致斑块破裂的促炎机制的关键效应物。大量报告证实了这些因子在循环血液中和斑块局部的重要性。然而，对于导致这些紊乱的分子机制以及 ACS 的标准治疗对这些过程的影响，我们知之甚少。本研究的目的是评估 MMP-2、MMP-9 和 TIMP-2 的基因表达，并评估标准治疗对研究基因表达的影响。该研究纳入了 32 名 ACS 患者和 15 名健康受试者（对照组）。使用 Rosette-Sep 试剂盒分离单核细胞。在研究组中于第 1 天和第 5 天评估 MMP-2、MMP-9 和 TIMP-2 的基因表达，并在对照组中进行一次评估。从单核细胞中提取总 mRNA，并通过 QRT-PCR 评估 mRNA 拷贝数。与健康对照组相比，ACS 患者的单核细胞中 MMP-2、MMP-9 和 TIMP-2 的基因表达明显更高（0.0915±0.037 对 0.001±0.0002，p<0.01；0.81±0.279 对 0.10±0.057，p<0.05；0.84±0.140 对 0.42±0.126，p<0.05）。经过 5 天的标准治疗后，MMP-2 基因表达显著下降。在观察期间，其他研究基因没有发生相关变化。经典动脉粥样硬化危险因素与研究基因的表达之间未发现显著相关性。ACS 患者的单核细胞明显过度表达 MMP-2、MMP-9 和 TIMP-2。5 天的标准治疗导致 MMP-2 基因下调。MMP 基因的过度表达似乎是 ACS 发病机制的一个独立因素。
