Therapeutic potential of matrix metalloproteinase inhibitors in atherosclerosis

The activity of matrix-degrading metalloproteinases (MMPs) is essential for many of the processes involved in atherosclerotic plaque formation, for ex ample, infiltration of inflammatory cells, smooth muscle cell migration and proliferation and angiogenesis. Furthermore, matrix degradation by MMPs ma y cause the plaque instability and rupture that leads to the clinical sympt oms 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 regul ated in normal blood vessels. The increased MMP activity during atheroscler otic plaque development and instability must therefore be caused by increas ed cytokine and growth factor-stimulated gene transcription, elevated zymog en activation and an imbalance in the MMP:TIMP ratio. It is therefore conce ivable 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 o f such an approach.