Matrix metaloproteinases in vascular pathology

Vascular diseases are the main cause of morbidity and mortality. The vascular extracellular matrix (ECM) is essential in mechanical support, also regulating the cellular behavior fundamental to vascular function and homeostasis. Vascular remodeling is an adaptive response to various physiological and pathological changes and is associated with aging and vascular diseases. The aim of this review is provide a general overview of the involvement of MMPs in the pathogenesis of vascular diseases, namely, arterial hypertension, atherosclerosis, aortic aneurysms and myocardial infarction. The change in the composition of the ECM by matrix metalloproteinases (MMPs) generates a pro-inflammatory microenvironment that modifies the phenotypes of endothelial cells and vascular smooth muscle cells. They play a central role in morphogenesis, tissue repair and remodeling in response to injury, e.g., after myocardial infarction, and in progression of diseases such as atherosclerosis. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension and aneurysm formation. MMPs are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio generally determines the extent of ECM protein degradation and tissue remodeling. Studies are currently focused on improving the diagnostic and prognostic value of MMPs involved in the pathogenic process, increasing their therapeutic potential, and monitoring the disease. New selective MMP inhibitors may improve the specificity of these inhibitors, target specific MMPs in relevant pathological conditions and mitigate some of the side effects.