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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2108.)
© 2008 American Heart Association, Inc.

Brief Reviews

Metalloproteinase Expression in Monocytes and Macrophages and its Relationship to Atherosclerotic Plaque Instability

Andrew C. Newby

From the Bristol Heart Institute, University of Bristol, UK.

Correspondence to Prof Andrew C. Newby, Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK. E-mail A.Newby{at}bris.ac.uk

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.

Overproduction of matrix metalloproteinases from macrophages plays a role in plaque rupture and myocardial infarction. Freshly recruited monocytes use a PG-dependent pathway to coordinately upregulate a highly destructive spectrum of MMPs. Resident macrophages rely on a series of pathways, including activation of nuclear factor B, to achieve graded upregulation of MMPs.

Key Words: atherosclerosis • inflammation • proteolysis • gene regulation

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