Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins.
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.
Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. angela.pirillo@guest.unimi.it
Angela
A
Pirillo
Patrizia
P
Uboldi
Nicola
N
Ferri
Alberto
A
Corsini
Hartmut
H
Kuhn
Alberico Luigi
AL
Catapano
D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D053440:Lipoproteins, HDL3 / Q000737:chemistry / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis*; D015854:Up-Regulation
D053440:Lipoproteins, HDL3; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D001093:Arachidonate 15-Lipoxygenase