Elastinolytic matrix metalloproteinases and their inhibitors as therapeutic targets in atherosclerotic plaque instability.
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.
Smeglin
Anthony
A
Department of Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
Frishman
William H
WH
D000789:Angina, Unstable / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases