title: Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation.
abstract: Atherosclerotic plaque rupture provokes most myocardial infarctions. Matrix metalloproteinases (MMPs) have counteracting roles in intimal thickening, which stabilizes plaques, on the one hand and extracellular matrix destruction that leads to plaque rupture on the other. This review briefly summarizes the key points supporting the involvement of individual MMPs in provoking plaque rupture and discusses the barriers that stand in the way of clinical translation, which can be itemised as follows: structural and functional complexity of the MMP family; lack of adequate preclinical models partly owing to different expression patterns of MMPs and TIMPs in mouse and human macrophages; the need to target individual MMPs selectively; the difficulties in establishing causality in human studies; and the requirement for surrogate markers of efficacy. Overcoming these barriers would open the way to new treatments that could have a major impact on cardiovascular mortality worldwide.
authors: University of Bristol, School of Clinical Sciences and Bristol Heart Institute, Bristol, UK. Electronic address: a.newby@bris.ac.uk.
authors: Andrew C
authors: AC
authors: Newby
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009203:Myocardial Infarction / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: Atherosclerosis; Cardiovascular disease; Inflammation; Macrophages; Stroke; Vascular smooth muscle