title: Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance.
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.
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Paulin
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Einthoven Laboratory for Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kooijman
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Xavier
authors.initials: X
authors.lastname: Blanchet
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; Department of Pathology, AMC, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Joana R
authors.initials: JR
authors.lastname: Viola
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; Department of Pathology, AMC, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: de Jong
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mandl
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; Department of Pathology, AMC, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hendrikse
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schiener
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Hundelshausen
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der LMU München, Munich 80336, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; DZHK, Partner Site Munich Heart Alliance, Munich 80336, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Khalil
authors.initials: K
authors.lastname: Bdeir
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der LMU München, Munich 80336, Germany; Institute for Diabetes and Regeneration, Helmholtz Center Munich, Germany; German Center for Diabetes Research (DZD) München-Neuherberg, Germany.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Hofmann
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Einthoven Laboratory for Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Patrick C N
authors.initials: PCN
authors.lastname: Rensen
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; Department of Pathology, AMC, 1105 AZ Amsterdam, The Netherlands; DZHK, Partner Site Munich Heart Alliance, Munich 80336, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich 80336, Germany; Department of Pathology, AMC, 1105 AZ Amsterdam, The Netherlands; DZHK, Partner Site Munich Heart Alliance, Munich 80336, Germany. Electronic address: oliver.soehnlein@gmail.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D011485:Protein Binding; D034622:RNA Interference; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D023084:alpha-Defensins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D023084:alpha-Defensins; C406413:human neutrophil peptide 1
keywords: Atherosclerosis; Human neutrophil peptide; Hypercholesterolemia; LDL receptor; Neutrophil