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Paulin, Nicole; Döring, Yvonne; Kooijman, Sander; Blanchet, Xavier; Viola, Joana R.; Jong, Renske de; Mandl, Manuela; Hendrikse, Jeffrey; Schiener, Maximilian; Hundelshausen, Philipp von; Vogt, Anja; Weber, Christian; Bdeir, Khalil; Hofmann, Susanna M.; Rensen, Patrick C. N.; Drechsler, Maik; Soehnlein, Oliver (2017): Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance. In: Ebiomedicine, Vol. 16: pp. 204-211
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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. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).