Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance

Autor: Nicole Paulin, Yvonne Döring, Sander Kooijman, Xavier Blanchet, Joana R. Viola, Renske de Jong, Manuela Mandl, Jeffrey Hendrikse, Maximilian Schiener, Philipp von Hundelshausen, Anja Vogt, Christian Weber, Khalil Bdeir, Susanna M. Hofmann, Patrick C.N. Rensen, Maik Drechsler, Oliver Soehnlein
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: EBioMedicine, Vol 16, Iss C, Pp 204-211 (2017)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2017.01.006
Popis: Increases in plasma LDL-cholesterol have unequivocally been established as a causal risk factor for atherosclerosis. Hence, strategies for lowering of LDL-cholesterol may have immediate therapeutic relevance. Here we study the role of human neutrophil peptide 1 (HNP1) in a mouse model of atherosclerosis and identify its potent atheroprotective effect both upon transgenic overexpression and therapeutic delivery. The effect was found to be due to a reduction of plasma LDL-cholesterol. Mechanistically, HNP1 binds to apolipoproteins enriched in LDL. This interaction facilitates clearance of LDL particles in the liver via LDL receptor. Thus, we here identify a non-redundant mechanism by which HNP1 allows for reduction of LDL-cholesterol, a process that may be therapeutically instructed to lower cardiovascular risk.
Databáze: Directory of Open Access Journals