The extracellular matrix (ECM) contains a variety of structural proteins which include collagens, proteoglycans and glycoproteins. These proteins act as a cellular ‘skeleton’ allowing cell to cell interactions.
Physiologically, matrix remodelling requires the synthesis of matrix which is balanced by degradation mediated via the production of active matrix metalloproteinases (MMPs). When this balance of synthesis and degradation is uncontrolled, inadequate or increased amounts of ECM are deposited. Reduced levels of matrix are associated with unstable angina whereas elevated levels of matrix are found in alcoholic cirrhosis, pulmonary fibrosis and left ventricular hypertrophy (LVH).
To date, 17 MMPs have been characterized (Table 37.1). MMPs were originally classified in terms of their substrate specificity, but this view has now been superseded and a numbering system introduced when it was appreciated that each MMP could hydrolyse a variety of substrates, including the degradation of other MMPs.
MMPs have a variety of domains, but all MMPs share three: (i) a predomain which targets the MMP for extracellular excretion; (ii) a prodomain which maintains the MMP in an inactive form called the proMMP; and (iii) a zinc-dependent catalytic domain which becomes activated on hydrolysis of the prodomain. With the exception of MMP7, all the MMPs have a haemopexin domain which enhances the binding of substrates and inhibitors. MMPs contain two conserved motifs: the prodomain and catalytic domain. MMP14, 15, 16 and 17 have a transmembrane domain and MMP14 activates proMMP2 into its biologically active form .