title: Neutrophil-derived cathelicidin protects from neointimal hyperplasia.
abstract: Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University München, Munich 80336, Germany. oliver.soehnlein@med.uni-muenchen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Sarawuth
authors.initials: S
authors.lastname: Wantha
authors.forename: Sakine
authors.initials: S
authors.lastname: Simsekyilmaz
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
authors.forename: Remco T A
authors.initials: RT
authors.lastname: Megens
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Mause
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Ralf
authors.initials: R
authors.lastname: Smeets
authors.forename: Stefan
authors.initials: S
authors.lastname: Weinandy
authors.forename: Fabian
authors.initials: F
authors.lastname: Schreiber
authors.forename: Thomas
authors.initials: T
authors.lastname: Gries
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
authors.forename: Martin
authors.initials: M
authors.lastname: Möller
authors.forename: Santosh
authors.initials: S
authors.lastname: Vijayan
authors.forename: Marc A M J
authors.initials: MA
authors.lastname: van Zandvoort
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.forename: Christine T
authors.initials: CT
authors.lastname: Pham
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Doris
authors.initials: D
authors.lastname: Klee
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000601:surgery; D002478:Cells, Cultured; D054855:Drug-Eluting Stents; D006965:Hyperplasia / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D058426:Neointima / Q000517:prevention & control*; D009504:Neutrophils / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D001057:Apolipoproteins E; D054804:Cathelicidins