Nanni Samuele, Melandri Giovanni, Hanemaaijer Roeland, Cervi Vittorio, Tomasi Luciana, Altimari Annalisa, Van Lent Natascha, Tricoci Pierluigi, Bacchi Letizia, Branzi Angelo
Institute of Cardiology, Policlinico S. Orsola-Malpighi of Bologna, Italy.
Transl Res. 2007 Mar;149(3):137-44. doi: 10.1016/j.trsl.2006.09.001.
Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD. The distribution of MMP-3 5A/6A and MMP-9 C/T promoter polymorphisms and MMP-9 A/G exon-6 polymorphism were investigated in 200 consecutive male premature CAD patients (aged < or = 55 years) and 201 age-matched male blood donors. Plasma concentrations/activities of MMP-2 and MMP-9 were also measured, as were plasma concentrations of MMP-3, TIMP-1, and TIMP-2 in 80 patients (49 with ACSs and 31 with stable CAD) and 40 controls. Inflammation markers were also obtained. MMP genetic polymorphism distributions did not vary between patients and controls and did not seem to influence their respective MMP plasma levels. Patients showed increased MMP-9 and TIMP-1 concentrations and decreased TIMP-2 concentration and MMP-2 total activity (all P < or = 0.002). Overall, TIMP-1 correlated with C-reactive protein (CPR) (r = 0.594, P < 0.001) and haptoglobin (r = 0.276, P = 0.005), whereas MMP-2 activity correlated inversely with haptoglobin (r = -0.195, P = 0.032). Blood glucose correlated positively with TIMP-1 concentration (r = 0.711, P < 0.001) and negatively with MMP-2 activity (r = -0.250, P = 0.006). In conclusion, MMP and TIMP plasma levels in premature CAD are linked to clinical presentation and markers of inflammation and metabolic disorders rather than to genetic polymorphisms.
基质金属蛋白酶（MMPs）被认为参与冠状动脉疾病（CAD）的发病机制，尤其是急性冠状动脉综合征（ACS）的发生。关于CAD患者体内MMP的调控知之甚少。本研究评估了早发CAD患者中MMPs及其组织抑制剂（TIMPs）的表达和调控情况。研究了200例连续的男性早发CAD患者（年龄≤55岁）和201例年龄匹配的男性献血者中MMP - 3 5A/6A和MMP - 9 C/T启动子多态性以及MMP - 9 A/G外显子6多态性的分布情况。还测量了80例患者（49例ACS患者和31例稳定CAD患者）及40例对照者的血浆MMP - 2和MMP - 9浓度/活性，以及血浆MMP - 3、TIMP - 1和TIMP - 2的浓度。同时获取了炎症标志物。患者与对照者之间MMP基因多态性分布无差异，且似乎不影响各自的MMP血浆水平。患者的MMP - 9和TIMP - 1浓度升高，TIMP - 2浓度降低，MMP - 2总活性降低（均P≤0.002）。总体而言，TIMP - 1与C反应蛋白（CPR）相关（r = 0.594，P < 0.001）和触珠蛋白相关（r = 0.276，P = 0.005），而MMP - 2活性与触珠蛋白呈负相关（r = -0.195，P = 0.032）。血糖与TIMP - 1浓度呈正相关（r = 0.711，P < 0.001），与MMP - 2活性呈负相关（r = -0.250，P = 0.006）。总之，早发CAD患者血浆中MMP和TIMP水平与临床表现、炎症及代谢紊乱标志物相关，而非与基因多态性相关。
