Elastinolytic matrix metalloproteinases and their inhibitors as therapeutic targets in atherosclerotic plaque instability.
Elastinolytic matrix metalloproteinases and their inhibitors as therapeutic targets in atherosclerotic plaque instability.
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DOI：
10.1097/01.crd.0000105000.46909.81
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发表时间：
2004-05-01
影响因子：
2.1
通讯作者：
Frishman, William H
中科院分区：
文献类型：
--
作者：
Smeglin, Anthony;Frishman, William H
动脉粥样硬化是一个动态的病理过程，涉及许多细胞类型和化学介质之间的相互作用。在文献中有越来越多的证据表明基质金属蛋白酶，特别是那些具有弹性蛋白溶解活性的基质金属蛋白酶，与动脉粥样硬化斑块不稳定性有关。最近的研究结果还表明，基质金属蛋白酶及其抑制剂之间的平衡有助于细胞外基质的完整性，并且失衡可能是脑和心脏缺血事件的预先决定因素。大量证据表明，弹性蛋白分解基质金属蛋白酶及其抑制剂之间的平衡参与了动脉粥样硬化的过程。研究调查药物治疗，抑制基质金属蛋白酶或增加其天然抑制剂水平表明，抗动脉粥样硬化和潜在的斑块稳定的好处。必须完成精心设计的临床试验，以更好地了解这些酶的功能和相互作用，以开发选择性治疗方法来预防动脉粥样硬化的进展和并发症。
Atherosclerosis is a dynamic pathologic process involving interactions between many cell types and chemical mediators. There is increased evidence in the literature that matrix metalloproteinases, especially those with elastolytic activity, are associated with atherosclerotic plaque instability. Results of recent studies also suggest that the balance between matrix metalloproteinases and their inhibitors contributes to the extracellular matrix integrity, and an imbalance could be a predeterminate of both cerebral and cardiac ischemic events. Significant evidence demonstrates that the balance between elastolytic matrix metalloproteinases and their inhibitors are involved in the atherosclerotic process. Studies investigating pharmacologic therapies that inhibit matrix metalloproteinases or increase their natural inhibitor levels suggest an antiatherosclerotic and potential plaque-stabilizing benefit. Carefully designed clinical trials must be completed to better understand the functions and interactions of these enzymes with the goal of developing selective therapies to prevent the progression and complications of atherosclerosis.