Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

“…As already said, MMPs are important zinc-dependent endoproteases involved in both physiological and pathological ECM remodelling [ 13 ]. For instance, they are involved in reproductive growth, embryonic development and morphogenesis during pregnancy, bone remodelling, tissue repair, and wound healing [ 14 ]. Being produced as zymogens, their net activity on tissues is a careful balance between activation processes and inhibition by specific inhibitors (tissue inhibitors of matrix metalloproteinases, TIMPs) and not specific ones (e.g., α2-macroglobulin) [ 15 ].…”

“…Collagenases and gelatinases alter the molecules of the basal lamina, subsequently leading to cell death. In particular, collagenases degrade triple-helical fibrillar collagen in bone and ligaments, whereas gelatinases are involved in different cellular processes including angiogenesis and neurogenesis [ 14 ]. Stromelysins are small proteases that degrade segments of the ECM, and matrilysins process cell surface molecules and digest ECM components [ 14 ].…”

“…In particular, collagenases degrade triple-helical fibrillar collagen in bone and ligaments, whereas gelatinases are involved in different cellular processes including angiogenesis and neurogenesis [ 14 ]. Stromelysins are small proteases that degrade segments of the ECM, and matrilysins process cell surface molecules and digest ECM components [ 14 ]. Finally, MT-MMPs have collagenolytic activity and may activate some proteases and components of the cell surface [ 24 , 25 ].…”

“…MMPs are maintained into an inactive form by a pro-peptide domain, which should be removed to convert the enzyme into the active form, an event that usually happens in the extracellular space through other proteolytic enzymes such as serine proteases, plasmin, or other MMPs [ 14 ]. As an exception, some MMPs have a furin recognition site before the catalytic domain, allowing the intracellular activation of the enzyme by furin [ 10 , 21 ].…”

“…Once synthesized, the activity of MMPs depends on the activation of their latent form as well as on endogenous tissue inhibitors, namely α2-macroglobulins and TIMPs [ 22 ], which bind to the enzymes suppressing the activity. When the activity is not well-balanced by a fine-tuned inhibition, a transition from physiological to pathological condition occurs [ 14 ].…”