Matrix metalloproteinases(MMPs) are a family of structurally related zinc endopeptidases capable of proteolysis of   numerous composition of  the extracellular matrix(ECM). Recent studies show that they play major roles not only in ECM   degradation but also in mediating cell-cell adhesion, cell migration and invasion, cell proliferation and apoptosis,     tissue remodeling, and growth factor and cytokine signaling. MMPs are divided into three subclasses, including           interstitial collagenases, gelatinases and stromelysins.

    We have examined the expression of different circulating MMPs in patients with or without angiographically proven    coronary artery disease. We found plasma MMP-2,-3 and -9 levels were all increased in CAD patients when compared with    cardiac syndrome X as well as normal subjects. The plasma MMP-3 was a novel predictor of adverse cardiovascular events in stable CAD patients. We also developed a risk score to evaluate the clinical implication of plasma MMPs in stable CAD.

    In order to understand the relationship between MMPs and restenosis, we use endothelia-denudated hypercholesterolemic rabbits as an animal model. The endothelia-denudated hypercholesterolemic rabbits showed increased expression activity of MMPs than control subjects without high cholesterol diet-fed. The lipid-lowering agent, probucol, significant inhibited  the expression and activity of MMPs in endothelia-denudated hypercholesterolemic rabbits. Carvedilol, a beta-adrenoceptor and alpha-adrenoceptor antagonist with potent antioxidant property, could have the same effects on the expression and    activity of MMPs in these animals.

    In summary, we demonstrate the clinical implication of MMPs in stable CAD and the role of MMPs in vascular restenosis through animal model, suggesting its potential role in atherosclerosis.
 
    基质金属蛋白酶（MMPs）是一类结构上与锌肽链内切酶相关的家族，能够蛋白水解多种细胞外基质成分。最近研究表明其不但在细胞外基质降解中有主要作用，而且可以介导细胞与细胞间的粘附，细胞迁移，细胞增殖与调亡，组织重建，以及生长因子和细胞因子信号传导。MMPs可以分为三个亚类，包括空隙胶原酶，明胶酶，以及基质水解酶。

    我们检测了血管造影证实有或没有冠心病的病人的循环MMPs表达情况。发现冠心病患者的血浆MMP-2,-3 和 -9水平较冠状动脉综合征X患者以及正常人高。血浆MMP-3是一种新发现的稳定型冠心病患者发生心血管事件的指标。我们还建立了危险分数来评价血浆MMP-3在稳定型冠心病患者中的临床意义。

    为了了解MMPs与血管再狭窄的关系，我们以内皮裸露的高胆固醇兔为动物模型，发现高胆固醇兔的MMPs的表达活性较无高胆固醇饮食的对照组增高。低密度脂蛋白和probucol可明显抑制内皮裸露的高胆固醇兔的MMPs的表达和活性。β-肾上腺受体和α-肾上腺受体阻滞剂，卡地洛尔具有潜在的抗氧化特性，在这些动物模型中对MMPs的表达和活性有相同的作用。

    总之，我们通过动物模型证实了MMPs在稳定型冠心病中的临床意义，以及其在血管再狭窄中的作用，表明了MMPs在动脉粥样硬化中的潜在作用。