Atherosclerosis: Neutrophil-derived cathelicidin protects from neointimal hyperplasia

Oliver Soehnlein, Sarawuth Wantha, Sakine Simsekyilmaz, Yvonne Döring, Remco T.A. Megens, Sebastian F. Mause, Maik Drechsler, Ralf Smeets, Stefan Weinandy, Fabian Schreiber, Thomas Gries, Stefan Jockenhoevel, Martin Möller, Santosh Vijayan, Marc A.M.J. Van Zandvoort, Birgitta Agerberth, Christine T. Pham, Richard L. Gallo, Tilman M. Hackeng, Elisa A. LiehnAlma Zernecke, Doris Klee, Christian Weber

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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 neutrophilborne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation.We then translated these findings to an animalmodel using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coatedwith LL-37. This stent reduced in-stent stenosis in amousemodel of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.

Original languageEnglish
JournalScience translational medicine
Volume3
Issue number103
DOIs
StatePublished - Oct 5 2011

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