Atherosclerosis is a major contributor to worldwide mortality and is characterized by narrowing of the arteries due to a thickening of the vessel wall. This restricts blood supply to the tissues and can lead to heart attack or stroke. In many cases, implantation of a stent can successfully be used for revascularization of the obstructed or stenosed arteries to improve blood flow. However, when a regrowth of cells occurs in the inner vessel wall (the intima) or healing of the endothelial cell lining in the vessel lumen is incomplete, the result can be a restenosis, i.e. recurrent arterial obstruction and restriction of blood flow.
A research team led by LMU's Professor Christian Weber has now shown that a specific cell type called neutrophils, and molecules that they secrete, inhibit this life-threatening complication – which is observed in up to one-third of all stent implantations.
One of the products secreted by neutrophils, a short peptide named cathelicidin, promotes the healing of damaged blood vessels and patency of the stents by improving endothelial cell recovery, and prevents the formation of so-called neointima, which consists of cells of the inner vessel wall that contribute to restenosis at the site of stent implantation. Indeed, experiments in mice demonstrated that the incidence of restenosis was significantly reduced when miniaturized stents were coated with the peptide.
"Most modern stents release compounds aiming to block cell growth and inhibit inflammation – nevertheless restenoses and other serious complications, such as thromboses, can still occur ," says Weber, Director of the Institute for Cardiovascular Prevention at Munich University Medical Center. "We hope that cathelicidin-coated stents have the expected effect in human subjects. Moreover, we plan to use our model systems to test the effects of other products secreted by neutrophils, as well as other peptides with similar functions to cathelicidin."
The project was carried out under the auspices of Collaborative Research Program 809 (Chemokines in Cardiovascular Pathogenesis), which is funded by the Deutsche Forschungsgemeinschaft (DFG). (suwe/PH) (Science Translational Medicine online, 5. October 2011)
Publication:
Neutrophil-derived cathelicidin protects from neointimal hyperplasia
Oliver Söhnlein et al.
Science Translational Medicine online, 5. October 2011
Contact:
Professor Christian Weber
Institute for Prophylaxis and Epidemiology of Cardiovascular Diseases
Munich University Medical Center
Phone: +49 89 5160 4351
Fax: +49 89 5160 4352
Email: kreislaufinstitut@med.uni-muenchen.de
Web: www.kreislaufinstitut.de
Journal
Science Translational Medicine