Matrix Metalloproteinases in Atherothrombosis

Abstract 

The metalloproteinases (MMPs, matrixins) are zinc-containing endopeptidases involved in the metabolism of extracellular matrix as well as in the cleavage of other proteins. The MMP family currently consists of 28 enzymes with somewhat different activities. The members are in part categorized into groups according to either structure or preferred substrates and referred to as collagenases, gelatinases, stromelysins, matrilysins, and membrane-bound MMPs. The proteinase activities exerted by 11 of the 28 MMPs have been implicated in some of the biologic processes associated with atherosclerosis and its ischemic clinical manifestations such as myocardial infarction and stroke. For example, several of the MMPs are locally expressed within human atherosclerotic lesions. However, association studies of subclinical atherosclerosis have generated contradictory results in the role of MMP activities. In addition, circulating MMP levels as well as genetic variations within the genes encoding the different enzymes have been associated with both an increased and decreased cardiovascular risk. Finally, experimental studies of hyperlipemic mice and vascular injury have suggested some of the MMPs function as modulators of atherogenesis, vascular remodeling, and plaque rupture.

Abbreviations and Acronyms: 5A, 5 adenosines, 6A, 6 adenosines, ApoE, apolipoprotein E, ApoE^−/−, ApoE knockout, CAD, coronary artery disease, CRP, C-reactive protein, ET-1, endothelin-1, IFN-γ, interferon gamma, IL-10, interleukin 10, IL1-β, interleukin β, IL-4, interleukin 4, IL-6, interleukin 6, IL-8, interleukin 8, LPS, lipopolysaccharide, MI, myocardial infarction, MMP, matrix metalloproteinase, mRNA, messenger ribonucleic acid, NGAL, neutrophil gelatinase-associated lipocalin, PAOD, peripheral arterial occlusive disease, SMC, smooth muscle cell, SNP, single-nucleotide polymorphism, TGF-β1, transforming growth factor β-1, TIMP, tissue inhibitor of metalloproteinases, TNF-α, tumor necrosis factors-α, UA, unstable angina

Keyword: Atherosclerosis, Collagenase, Gelatinase, Inflammation, Lipoxygenase, Myocardial infarction