Matrix Metalloproteinases

MMPs serve to regulate the extracellular environment through breakdown and proteolysis of matrix components, so as to facilitate a favorable environment for cellular development. MMPs are produced in a propeptide form and undergo eventual cleavage in the extracellular environment. MMPs have been implicated in processes such as neointimal hyperpla-sia, left ventricular remodeling, and formation of vascular aneurysms.

MMP-9, or gelatinase B, and MMP-2, or gelatinase A, are thought to be involved in the development of plaque instability. Local release of these factors is believed to degrade the fibrous cap of the atherosclerotic plaque. Evidence to support the involvement of MMPs in ACS has come from small clinical studies. Higher blood levels of MMP-2 and MMP-9 have been noted in ACS patients compared with healthy controls. Although elevated MMP-9 concentrations were associated with an increased hazard ratio of cardiovascular death after adjusting for clinical confound-ers,24 what was not entirely evident was whether MMP-9 provided prognostic information beyond that conveyed by other biomarkers of inflammation typically examined in ACS. Although preliminary work with MMPs is suggestive of their participation in ACS, future translational and clinical investigations need to examine not only MMPs but also their relationship with tissue inhibitors of metalloprotein-ases (TIMPs). This regulatory association is important, and an improved understanding of it may provide more accurate and more valuable insight as to the significance of MMPs/TIMPs in coronary atherosclerosis and ACS.

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