Document Detail

Neutrophil-derived cathelicidin protects from neointimal hyperplasia.
MedLine Citation:
PMID:  21974936     Owner:  NLM     Status:  MEDLINE    
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.
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 Liehn; Alma Zernecke; Doris Klee; Christian Weber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  3     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-06     Completed Date:  2012-05-01     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  103ra98     Citation Subset:  IM    
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MeSH Terms
Antimicrobial Cationic Peptides / chemistry,  therapeutic use*
Apolipoproteins E / genetics
Atherosclerosis / surgery
Cells, Cultured
Drug-Eluting Stents
Hyperplasia / prevention & control*
Mice, Knockout
Neointima / prevention & control*
Neutrophils / metabolism*
Grant Support
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Apolipoproteins E; 143108-26-3/CAP18 lipopolysaccharide-binding protein
Comment In:
Nat Rev Drug Discov. 2011 Dec;10(12):902   [PMID:  22129987 ]

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