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

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 atheroscler...

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Detalles Bibliográficos
Autores principales: Paulin, Nicole, Döring, Yvonne, Kooijman, Sander, Blanchet, Xavier, Viola, Joana R., de Jong, Renske, Mandl, Manuela, Hendrikse, Jeffrey, Schiener, Maximilian, von Hundelshausen, Philipp, Vogt, Anja, Weber, Christian, Bdeir, Khalil, Hofmann, Susanna M., Rensen, Patrick C.N., Drechsler, Maik, Soehnlein, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474437/
https://www.ncbi.nlm.nih.gov/pubmed/28111237
http://dx.doi.org/10.1016/j.ebiom.2017.01.006
Descripción
Sumario: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.

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