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

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:

دوره 16  شماره 

صفحات  -

تاریخ انتشار 2017