Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability.
Matrix metalloproteinases (MMPs) can degrade strength-giving collagens and other structural proteins of the arterial extracellular matrix. Overproduction of MMPs by monocyte/macrophages could therefore promote atherosclerotic plaque rupture and myocardial infarction. Freshly-recruited monocyte macrophages appear to use a prostaglandin (PG)-dependent pathway to coordinately upregulate a broad and potentially highly-destructive spectrum of MMPs. Differentiated macrophages rely on a series of distinct pathways to selectively upregulate groups of MMPs. Moreover, recent evidence suggests that different macrophage phenotypes express characteristically different spectra of MMPs and their inhibitors. New therapies may result from targeting matrix MMP overproduction.
Newby
Andrew C
AC
Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK. A.Newby@bris.ac.uk
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000201:enzymology; D005487:Foam Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D045726:Metalloproteases / Q000378:metabolism*; D008955:Models, Cardiovascular; D009000:Monocytes / Q000201:enzymology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D016328:NF-kappa B; D019714:Tissue Inhibitor of Metalloproteinases; D015847:Interleukin-4; D045726:Metalloproteases