Human neutrophil elastase: mediator and therapeutic target in atherosclerosis.
Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed.
Henriksen
Peter A
PA
Department of Cardiology, The Royal Infirmary of Edinburgh, Old Dalkeith Road, Edinburgh EH16 4SA, UK. p.henriksen@blueyonder.co.uk
Sallenave
Jean-Michel
JM
D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D053492:Elafin / Q000627:therapeutic use; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism* / Q000627:therapeutic use*; D008954:Models, Biological; D000515:alpha 1-Antitrypsin / Q000627:therapeutic use
D053492:Elafin; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase