title: Role of the endogenous elastase inhibitor, elafin, in cardiovascular injury: from epithelium to endothelium.
abstract: Neutrophils and neutrophil-derived elastases play a major role in the regulation of vascular injury and inflammation, such as ischemia-reperfusion injury. Elafin is an endogenous inhibitor of neutrophil-derived elastases with numerous anti-inflammatory functions that include modulation of inflammatory cytokine release as well as innate and adaptive immunity. It is produced by epithelial tissues including the skin and respiratory system that have adapted to respond to the microbial and chemical insults that lead to inflammation. The production of peptides like elafin with multi-faceted anti-inflammatory activity is an important part of this adaptation. Although not directly expressed within the cardiovascular system itself, pre-clinical studies have suggested therapeutic benefit of elafin in cardiovascular disease. The aim of this review is to highlight the role of neutrophil-derived elastases in vascular inflammation and injury. We will discuss the beneficial effects of elafin inhibition of neutrophil elastase and its extended anti-inflammatory activity in pre-clinical models of inflammatory vascular injury.
authors.affiliation: Cardiology Research Fellow, Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. s.r.alam-1@sms.ed.ac.uk
authors.forename: Shirjel R
authors.initials: SR
authors.lastname: Alam
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Peter A
authors.initials: PA
authors.lastname: Henriksen
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D053492:Elafin / Q000378:metabolism* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology; D011480:Protease Inhibitors / Q000627:therapeutic use; D051381:Rats; D013927:Thrombosis / Q000201:enzymology; D014657:Vasculitis / Q000201:enzymology
chemical_list: D016207:Cytokines; D053492:Elafin; D011480:Protease Inhibitors; D019272:Leukocyte Elastase