Putative targeting of matrix metalloproteinase-8 in atherosclerosis

There is compelling evidence indicating that some members of the matrix metalloproteinase (MMP) family play important roles in the pathogenesis of atherosclerosis and related vascular and cardiac conditions such as atherosclerotic plaque rupture leading to myocardial infarction, heart failure after myocardial infarction, neointima formation following angioplasty, and abdominal aortic aneurysm. Studies have shown that administration of MMP inhibitors can deter some of these conditions in experimental animal models, but few pertinent human clinical trials have been reported to date. Clinical studies of broad-spectrum MMP inhibitors in cancers and arthritis, however, have reported considerable side effects that are likely to be related to the lack of selectivity of these inhibitors. Since different members of the MMP family can have divergent and even opposing functions, it is believed that selective MMP inhibitors that specifically target particular MMPs that are key in the disease pathogenesis will likely have greater efficacy and less adverse effects. In recent years there has been accumulating evidence indicating an important role of MMP8 in atherosclerosis and the associated conditions mentioned above. This article will review findings from studies examining MMP8 in relation to these conditions and discuss rationale of targeting MMP8 as a potential therapeutic strategy. (C) 2014 Elsevier Inc. All rights reserved.