Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Via E. dal Pozzo, 06126, Perugia, Italy.
Intern Emerg Med. 2010 Feb;5(1):13-25. doi: 10.1007/s11739-009-0283-y. Epub 2009 Jul 21.
Matrix metalloproteinases (MMPs), a family of enzymes that degrade extracellular matrix, are emerging as important modulators of atherothrombosis. MMPs are produced by inflammatory cells; some of them are also released by activated platelets and play a crucial role in the remodeling processes, leading to atherosclerotic plaque formation, plaque rupture, arterial aneurysm development, and critical limb ischemia. Independent from their matrix degrading activity, MMPs also regulate some cell functions relevant to atherothrombosis, such as platelet activation, neutrophil activation, and vascular reactivity. Plasma levels of some MMPs are increasingly being recognized as a biomarker of atherosclerosis and cardiovascular risk. In peripheral arterial disease, MMPs have been shown to be involved in angiogenesis, arteriogenesis, and the development of arterial calcifications. Increased plasma levels of some MMPs (MMP-2, MMP-9) have been correlated with PAD development and severity. Single nucleotide polymorphisms of the genes encoding for some MMPs have also been associated with the risk of developing peripheral arterial disease and critical limb ischemia. Large prospective observational studies are needed to further demonstrate the role of MMPs in PAD. In perspective, pharmacologic targeting of the expression or activity of MMPs may represent a novel, attractive approach for the treatment of peripheral arterial disease.
基质金属蛋白酶（MMPs）是一类能够降解细胞外基质的酶，它们正成为动脉粥样血栓形成的重要调节剂。MMPs 由炎症细胞产生；其中一些也被激活的血小板释放，并在重塑过程中发挥关键作用，导致动脉粥样硬化斑块形成、斑块破裂、动脉瘤发展和肢体严重缺血。独立于其基质降解活性，MMPs 还调节与动脉粥样血栓形成相关的一些细胞功能，如血小板激活、中性粒细胞激活和血管反应性。某些 MMP 的血浆水平越来越被认为是动脉粥样硬化和心血管风险的生物标志物。在周围动脉疾病中，MMPs 被证明参与血管生成、动脉生成和动脉钙化的发展。一些 MMP（MMP-2、MMP-9）的血浆水平升高与 PAD 的发展和严重程度相关。编码某些 MMP 的基因的单核苷酸多态性也与发生外周动脉疾病和肢体严重缺血的风险相关。需要进行大型前瞻性观察性研究，以进一步证明 MMPs 在 PAD 中的作用。从前景看，针对 MMP 表达或活性的药物靶向治疗可能是治疗外周动脉疾病的一种有吸引力的新方法。
