Table 1.

Key MMPs that are synthesized by VSMCs and/or mediate ECM degradation in AAA.

	Expression	Enzyme Group	Substrate	Function
MMP-1	VSMCs, fibroblast, leukocytes	Collagenase	Collagen (I, II, III, VII, VIII, X), MMP-2, MMP-9, gelatin, proteoglycans	Released predominantly by mesenchymal cells [45,46]. Relies on presence of active MMP3 and plasmin to promote transition of proMMP-1 to active MMP-1 [46]
MMP-2	VSMCs, fibroblasts, macrophages	Gelatinase	Gelatin, collagens (I, IV, V, VII, X, XI, XIV), MMP-1, MMP-9, MMP-13, elastin, fibronectin, laminin	Degrades elastin and fibrillar collagen. Largely expressed by VSMCs [47,48]. Transition of contractile to synthetic VSMC phenotype (as seen in AAA) induces MMP-2 production and enables migratory properties [49]. Mediated by other MMPs (1, 7, membrane type MMPs) [50]
MMP-3	Fibroblasts, epithelial cells, macrophages	Stromelysin	Collagens (III, IV, V, IX, X), MMPs (1, 7, 8, 9, 13), fibronectin, gelatin, laminin	The 5A/6A polymorphism on the MMP-3 gene promoter region increased MMP-3 transcriptional activity and is an independent risk factor for AAA development [51]
MMP-9	VSMCs, fibroblasts, infiltrating macrophages	Gelatinase	Collagens (I, IV, V, VII, X, XI, XIV), elastin, fibronectin, plasminogen	Comprises the predominant elastases present in human AAA. Also exhibits collagenolytic and gelatinolytic activity [52]. Very low concentrations in cell cultures from normal aortic tissues [53]. Works in concert with MMP-2 and MMP-12 to promote aneurysmal degeneration [54,55]. MMP9 C-1562T polymorphism significantly more common in AAA compared to PVD patients and control subjects [52]
MMP-12	Macrophages	Collagenase	Collagen IV, MMP-2, gelatin, elastin, fibronectin, casein, plasminogen, fibrinogen	Increased in human AAA and not seen in atherosclerotic or normal media tissues. Activity is localized in the tunica media [56]. Genetic inactivation or pharmacological inhibition of PI3-kinase delta increased MMP-12 expression and macrophage migration [57]
MMP-13	VSMCs	Collagenase	Collagens (I, II, III, IV, IX, X, XIV), gelatin, MMP-9	Enzymatic activity is localized to VSMCs of aneurysms. -77A/G polymorphism was an independent risk factor for AAA formation [51]. Nitric oxide-induced CD147 production led to increased MMP13 expression in PPE-induced AAA mice [58]
MMP-14	VSMCs, macrophages	Membrane type	Collagens (I, II, III), MMP-2, gelatin, casein, elastin, vitronectin, fibronectin, laminin	Prominent activator of proMMP-2 [59]. Primarily degrades collagens type I, II, and III. To a lesser degree, degrades gelatin, casein, elastin, fibronectin, vitronectin, and laminin causing degradation of the ECM in the tunica media and adventitia [45,59,60]