Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance
Year: 2017
Type: article
Abstract: 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.
Source: EBioMedicine
Authors: 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
Institutions: Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität München, Leiden University Medical Center, Amsterdam UMC Location University of Amsterdam, LMU Klinikum, German Centre for Cardiovascular Research, University of Pennsylvania, Helmholtz Munich, German Center for Diabetes Research
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
OpenAlex ID: W2569366174