Neutrophil-derived cathelicidin protects from neointimal hyperplasia

Area of Science:

• Cardiovascular Research
• Biomaterials Science
• Immunology

Background:

• Drug-eluting stents (DES) are used to prevent in-stent stenosis after percutaneous transluminal angioplasty but can lead to late stent thrombosis.
• Endothelial recovery is crucial for optimal vascular healing after stenting, but current DES may impede this process.
• Neutrophils and their granule proteins play a role in arterial healing following injury.

Purpose of the Study:

• To investigate the role of neutrophil-derived cathelicidins in arterial healing after stent implantation.
• To evaluate the efficacy of a novel stent functionalized with cathelicidin LL-37 in preventing in-stent stenosis.

Main Methods:

• Examined the effect of neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) on reendothelization and neointima formation in injured arteries.
• Developed and tested a biofunctionalized Nitinol stent coated with LL-37 in a mouse model of atherosclerosis.

Main Results:

• Neutrophil cathelicidin LL-37 was found to promote reendothelization, thereby limiting neointima formation post-stent implantation.
• The LL-37-coated stent significantly reduced in-stent stenosis in a mouse model of atherosclerosis.
• LL-37 demonstrated a potential to enhance vascular healing after interventional therapy.

Conclusions:

• Neutrophil cathelicidin LL-37 is a key mediator of vascular healing after arterial injury.
• LL-37-eluting stents represent a promising therapeutic strategy to improve outcomes following coronary interventions.
• Targeting neutrophil-derived factors like LL-37 may offer a novel approach to overcome limitations of current stent technologies.