Brown Bethan A, Williams Helen, George Sarah J
School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Prog Mol Biol Transl Sci. 2017;147:197-237. doi: 10.1016/bs.pmbts.2017.01.004. Epub 2017 Mar 3.
Atherosclerosis leads to blockage of arteries, culminating in myocardial infarction, and stroke. The involvement of matrix-degrading metalloproteinases (MMPs) in atherosclerosis is established and many studies have highlighted the importance of various MMPs in this process. MMPs were first implicated in atherosclerosis due to their ability to degrade extracellular matrix components, which can lead to increased plaque instability. However, more recent work has highlighted a multitude of roles for MMPs in addition to breakdown of extracellular matrix proteins. MMPs are now known to be involved in various stages of plaque progression: from initial macrophage infiltration to plaque rupture. This chapter summarizes the development and progression of atherosclerotic plaques and the contribution of MMPs. We provide data from human studies showing the effect of MMP polymorphisms and the expression of MMPs in both the atherosclerotic plaque and within plasma. We also discuss work in animal models of atherosclerosis that show the effect of gain or loss of function of MMPs. Together, the data provided from these studies illustrate that MMPs are ideal targets as both biomarkers and potential drug therapies for atherosclerosis.
动脉粥样硬化会导致动脉阻塞，最终引发心肌梗死和中风。基质降解金属蛋白酶（MMPs）参与动脉粥样硬化已得到证实，许多研究强调了各种MMPs在这一过程中的重要性。MMPs最初被认为与动脉粥样硬化有关，是因为它们能够降解细胞外基质成分，这可能导致斑块稳定性增加。然而，最近的研究突出了MMPs除了分解细胞外基质蛋白之外的多种作用。现在已知MMPs参与斑块进展的各个阶段：从最初的巨噬细胞浸润到斑块破裂。本章总结了动脉粥样硬化斑块的发展和进展以及MMPs的作用。我们提供了来自人体研究的数据，显示了MMP多态性的影响以及MMPs在动脉粥样硬化斑块和血浆中的表达。我们还讨论了动脉粥样硬化动物模型中的研究工作，这些研究显示了MMPs功能获得或丧失的影响。这些研究提供的数据共同表明，MMPs作为动脉粥样硬化的生物标志物和潜在药物治疗靶点是理想的。
