Konstantino Yuval, Nguyen Tu T, Wolk Robert, Aiello Robert J, Terra Steven G, Fryburg David A
Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT, USA.
Biomarkers. 2009 Mar;14(2):118-29. doi: 10.1080/13547500902765140.
Matrix metalloproteinase (MMP)-9, a member of the MMP superfamily is consistently implicated in the pathophysiology of atherosclerosis and plaque rupture, the most common mechanism responsible for acute coronary syndrome (ACS).
To summarize the role of MMP-9 in atherosclerosis and its potential implications in assessment and treatment of coronary artery disease (CAD).
We reviewed the PubMed database for relevant data regarding the role of MMP-9 in the pathophysiology of atherosclerosis. In the light of these data, we postulate potential implications of MMP-9 in the management and treatment of CAD.
Existing data strongly support the role of MMP-9 in plaque destabilization and rupture. Based on the current knowledge, MMP-9 can potentially serve as a diagnostic biomarker in ACS and a prognostic biomarker in ACS and chronic CAD patients. MMP-9 is reduced by therapies that are associated with favourable outcome in atherosclerosis and thus may serve as a surrogate biomarker of treatment efficacy. However, large morbidity and mortality trials are still required to confirm that MMP-9 reduction is associated with improved outcome independent of the traditional risk factors (i.e. low-density lipoprotein cholesterol). Given its role in plaque rupture, inhibition of MMP-9 may promote plaque stabilization and consequently reduce cardiovascular events. Yet, the efficacy and safety of MMPs inhibitors should be first studied in preclinical models of atherosclerosis.
基质金属蛋白酶(MMP)-9是MMP超家族的成员之一,一直被认为与动脉粥样硬化的病理生理学以及斑块破裂有关,而斑块破裂是急性冠状动脉综合征(ACS)最常见的发病机制。
总结MMP-9在动脉粥样硬化中的作用及其在冠状动脉疾病(CAD)评估和治疗中的潜在意义。
我们在PubMed数据库中检索了有关MMP-9在动脉粥样硬化病理生理学中作用的相关数据。根据这些数据,我们推测了MMP-9在CAD管理和治疗中的潜在意义。
现有数据有力地支持了MMP-9在斑块不稳定和破裂中的作用。基于目前的认识,MMP-9有可能作为ACS的诊断生物标志物以及ACS和慢性CAD患者的预后生物标志物。与动脉粥样硬化良好预后相关的治疗可降低MMP-9水平,因此MMP-9可能作为治疗效果的替代生物标志物。然而,仍需要大规模的发病率和死亡率试验来证实,MMP-9的降低与独立于传统危险因素(即低密度脂蛋白胆固醇)的预后改善相关。鉴于其在斑块破裂中的作用,抑制MMP-9可能促进斑块稳定,从而减少心血管事件。然而,MMP抑制剂的疗效和安全性应首先在动脉粥样硬化的临床前模型中进行研究。