TY - JOUR
T1 - Neutrophil-Derived Cathelicidin Protects from Neointimal Hyperplasia
AU - Soehnlein, Oliver
AU - Wantha, Sarawuth
AU - Simsekyilmaz, Sakine
AU - Doering, Yvonne
AU - Megens, Remco T. A.
AU - Mause, Sebastian F.
AU - Drechsler, Maik
AU - Smeets, Ralf
AU - Weinandy, Stefan
AU - Schreiber, Fabian
AU - Gries, Thomas
AU - Jockenhoevel, Stefan
AU - Moeller, Martin
AU - Vijayan, Santosh
AU - van Zandvoort, Marc A. M. J.
AU - Agerberth, Birgitta
AU - Pham, Christine C. T. N.
AU - Gallo, Richard L.
AU - Hackeng, Tilman M.
AU - Liehn, Elisa A.
AU - Zernecke, Alma
AU - Klee, Doris
AU - Weber, Christian
PY - 2011/10/5
Y1 - 2011/10/5
N2 - 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 animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coatedwith 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.
AB - 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 animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coatedwith 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.
U2 - 10.1126/scitranslmed.3002531
DO - 10.1126/scitranslmed.3002531
M3 - Article
C2 - 21974936
SN - 1946-6234
VL - 3
SP - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 103
ER -