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Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins.

Abstract
Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is the main endothelial receptor for oxidized low density lipoprotein (OxLDL). LOX-1 is highly expressed in endothelial cells of atherosclerotic lesions, but also in macrophages and smooth muscle cells. LOX-1 expression is upregulated by several inflammatory cytokines (such as TNF-α), by oxidative stress, and by pathological conditions, such as dyslipidemia, hypertension, and diabetes. High density lipoprotein (HDL) possess several atheroprotective properties; however under pathological conditions associated with inflammation and oxidative stress, HDL become dysfunctional and exhibit pro-inflammatory properties. In vitro, HDL can be modified by 15-lipoxygenase, an enzyme overexpressed in the atherosclerotic lesions. Here we report that, after modification with 15-lipoxygenase, HDL(3) lose their ability to inhibit TNFα-induced LOX-1 expression in endothelial cells; in addition, 15LO-modified HDL(3) induce LOX-1 mRNA and protein expression and bind to LOX-1 with increased affinity compared to native HDL(3). Altogether these findings confirm that 15LO-modified HDL(3) possess a pro-atherogenic role.
AuthorsAngela Pirillo, Patrizia Uboldi, Nicola Ferri, Alberto Corsini, Hartmut Kuhn, Alberico Luigi Catapano
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 428 Issue 2 Pg. 230-3 (Nov 16 2012) ISSN: 1090-2104 [Electronic] United States
PMID23073138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Lipoproteins, HDL3
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • Arachidonate 15-Lipoxygenase
Topics
  • Arachidonate 15-Lipoxygenase (chemistry, metabolism)
  • Cells, Cultured
  • Endothelium, Vascular (metabolism)
  • Humans
  • Lipoproteins, HDL3 (chemistry, metabolism)
  • Scavenger Receptors, Class E (biosynthesis)
  • Up-Regulation

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