Metalloproteases in remodeling of vascular extracellular matrix

The matrix metalloproteinases (MMPs) constitute an ever growing family of related enzymes which degrade various components of the extracellular matrix (ECM). Since ECM catabolism is a basic requirement for tissue shaping early, during organ development, as well as later, during physiological and pathological remodeling, the action of MMPs is seemingly ubiquitous and recurring. This review will concentrate on the remodeling action of MMPs in the cardiovascular system: a topic which has come under scrutiny more recently. As in the case of other organs, the matrix-degrading action of vascular MMPs in the vessel wall can be both beneficial, by allowing their physiologic adaptation and healing, as well as detrimental, when assisting many of the pathologic processes ultimately leading to the structural destruction of blood vessels. These actions may be remarkably similar or overlap during the natural evolution of vascular diseases, to the point that it is often difficult to draw a line that clearly separates them. Vascular MMP production by normal cellular components of the healthy vessel wall is augmented and supplemented in pathological conditions by the contribution of inflammatory cells which infiltrate the diseased vessel wall. Many of the factors found to modulate the expression and enzymatic activation of MMPs in vitro, such as cytokines, growth factors, reactive oxygen species, are know to operate in the setting of atherosclerosis. Accordingly, the biology of vascular MMPs was examined with particular reference to atherosclerosis, a thoroughly-investigated pathological condition of the cardiovascular system.