Matrix metalloproteinases and their inhibitors in cardiovascular pathologies: current knowledge and clinical potential

Matrix metalloproteinases (MMPs) constitute a family of endopeptidases that harbor matrix-degrading potential, but also modulate the proliferation, migration, and apoptosis of resident blood-vessel cells and recruited inflammatory cells. Accordingly, they are proposed to play a major regulatory role in numerous cardiovascular pathologies, including restenosis, atherosclerosis, aneurysms, and post-myocardial infarction remodeling. Collectively, clinical and animal studies have begun to unravel the complex and often diverse effects MMPs and their endogenous tissue inhibitors of metalloproteinases (TIMPs) impart during cardiovascular pathologies. It is apparent that some MMPs are beneficial, while others impose detrimental influences on disease progression. This premise is underscored by evidence that broad-spectrum MMP inhibition fails to provide protection from most cardiovascular diseases. However, recent studies in mice using more selective inhibitors have proved promising. Consequently, there is an immediate need to elucidate the precise roles of individual MMPs and TIMPs in the distinct cardiovascular pathologies in order to facilitate the development and translation of new therapeutic approaches to combat cardiovascular disease, the major cause of death worldwide.