冠心病患者外周血单个核细胞基质金属蛋白酶9/组织型金属蛋白酶抑制剂1及磷酸化c-Jun蛋白表达改变与冠状动脉病变特征的相关性

目的 结合冠状动脉造影结果 ,探讨冠心病患者外周血单个核细胞基质金属蛋白酶9、组织型金属蛋白酶抑制剂1和磷酸化c-Jun蛋白表达水平改变与冠状动脉病变特征的关系.方法 40例经冠状动脉造影确诊的冠心病患者分为急性冠状动脉综合征组(n=24)和稳定型心绞痛组(n=16).另选取同期经冠状动脉造影证实无冠状动脉病变患者15例为对照组.采用免疫印迹法分别检测外周血单个核细胞基质金属蛋白酶9、组织型金属蛋白酶抑制剂1和磷酸化c-Jun蛋白表达水平,计算基质金属蛋白酶9/组织型金属蛋白酶抑制剂1比值,并结合Gensini冠状动脉病变积分标准评价其与冠状动脉管腔病变程度的线性关系及其在反映冠状动脉粥样硬化斑块稳定性中的作用.结果 ①急性冠状动脉综合征组基质金属蛋白酶9、组织型金属蛋白酶抑制剂1、磷酸化c-Jun蛋白表达水平及基质金属蛋白酶9/组织型金属蛋白酶抑制剂1比值较稳定型心绞痛组和对照组明显增高(均P<0.001).②基质金属蛋白酶9、磷酸化c-Jun及基质金属蛋白酶9/组织型金属蛋白酶抑制剂1比值与Gensini冠状动脉病变积分呈正相关(r分别为0.433、0.476和0.457,均P<0.01);组织型金属蛋白酶抑制剂1蛋白表达水平与Gensini冠状动脉病变积分无相关性.③磷酸化c-Jun与基质金属蛋白酶9蛋白表达水平呈显著正相关(r=0.839,P<0.001).结论 ①急性冠状动脉综合征患者基质金属蛋白酶9、组织型金属蛋白酶抑制剂1蛋白表达水平较稳定型心绞痛患者明显增高,其比例严重失调,反映了急性冠状动脉综合征患者冠状动脉管腔病变程度更为复杂且血管壁具有更多易损斑块;②核转录因子c-Jun活化可能参与了动脉粥样硬化中基质金属蛋白酶9表达的调控.

Correlations of Matrix Metalloproteinase-9/Metalloproteinase-1,Phospho-c-Jun Expression in Peripheral Blood Mononuclear Cells and the Characteristics of Atherosclerosis Plaque in Patients with Coronary Heart Disease

Aim To investigate the correlation between the protein expressions of matrix metailoproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and phospho-c-Jun in peripheral blood mononuclear cells of patients with coronary heart disease and the characteristics of atherosclerosis plaque combined with the coronary angiogra-phy. Methods 55 patients who had coronary heart disease and underwent an immediate or selective coronary angiog-raphy (CAG) were selected and divided into 3 groups: acute coronary syndrome (ACS) group (n=24), stable angina (SA) group (n=16) and conml group (n=15). MMP-9, TIMP-1 and phospho-c-Jun expressions in peripheral blood mononuclear cells were measured by Western-Blot. Coronary angiograms were scored according to Gensini integration and analysis of the relationship between MMP-9, TIMP-1, phospho-c-Jun, MMP-9/TIMP-1 and Gensini integration by linear correlation. Results ①MMP-9, TIMP-1, phospho-c-Jun and MMP-9/TIMP-1 were significantly increased in ACS group than those in SA group and control group (all P<0.001). ②MMP-9, phospho-c-Jun and MMP-9/TIMP-1 were positively correlated with Gensini integration (separately r=0.433, r=0.476, r=0.457, all P<0.01), but there was no correlation between TIMP-1 and Gensini integration. ③MMP-9 was greatly correlated with phospho-c-Jun in patients with coronary heart disease (r=0.839, P<0.001 ). Conclusions ①MMP-9 and MMP-9/TIMP-1 were significantly increased but imbalanced in the patients with ACS, which suggested a prediction of more complex damage and more vulner-able plaque in coronary artery. ②The activation of c-Jun may contribute to MMP-9 expression during the pathogenesis of atherosclerosis.