George S J
Bristol Heart Institute, Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, BS2 8HW, UK.
Expert Opin Investig Drugs. 2000 May;9(5):993-1007. doi: 10.1517/13543784.9.5.993.
The activity of matrix-degrading metalloproteinases (MMPs) is essential for many of the processes involved in atherosclerotic plaque formation, for example, infiltration of inflammatory cells, smooth muscle cell migration and proliferation and angiogenesis. Furthermore, matrix degradation by MMPs may cause the plaque instability and rupture that leads to the clinical symptoms of atherosclerosis; unstable angina, myocardial infarction and stroke. Together, the family of MMPs can degrade all of the components of the blood vessel extracellular matrix and their activity therefore, is tightly regulated in normal blood vessels. The increased MMP activity during atherosclerotic plaque development and instability must therefore be caused by increased cytokine and growth factor-stimulated gene transcription, elevated zymogen activation and an imbalance in the MMP:TIMP ratio. It is therefore conceivable that inhibition of MMPs or re-establishing the MMP:TIMP balance may be useful in treating the symptoms of atherosclerosis. Recent studies using synthetic MMP inhibitors and gene therapy have highlighted the potential of such an approach.
基质降解金属蛋白酶（MMPs）的活性对于动脉粥样硬化斑块形成所涉及的许多过程至关重要，例如炎症细胞浸润、平滑肌细胞迁移和增殖以及血管生成。此外，MMPs介导的基质降解可能导致斑块不稳定和破裂，进而引发动脉粥样硬化的临床症状，如不稳定型心绞痛、心肌梗死和中风。MMPs家族能够降解血管细胞外基质的所有成分，因此在正常血管中其活性受到严格调控。动脉粥样硬化斑块发展和不稳定过程中MMP活性的增加必定是由细胞因子和生长因子刺激的基因转录增加、酶原激活增强以及MMP与组织金属蛋白酶抑制因子（TIMP）比例失衡所致。因此可以设想，抑制MMPs或重新建立MMP与TIMP的平衡可能有助于治疗动脉粥样硬化的症状。近期使用合成MMP抑制剂和基因治疗的研究凸显了这种方法的潜力。
