Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by 15-lipoxygenase-modified LDL in endothelial cells.
OBJECTIVE
Lectin-like oxidized LDL receptor-1 (LOX-1), the endothelial receptor for OxLDL, is believed to be responsible for a number of OxLDL-induced effects in the endothelium.


RESULTS
In the present study we showed that LDL modified by 15-lipoxygenase (15LO-LDL), a form of minimally modified lipoprotein, beside its ability to induce pro-inflammatory responses such as oxidative stress and the expression of adhesion molecules, significantly increases LOX-1 expression in endothelial cells, both at transcriptional and at protein level. Such effect is likely to be mediated by p38 MAPK and NF-kB pathways. We then permanently overexpressed LOX-1 in an endothelial cell line and showed that 15LO-LDL were a ligand for LOX-1, and that the interaction LOX-1/15LO-LDL upregulated ICAM-1 surface expression.


CONCLUSIONS
Altogether these results indicate minimally modified LDL as a new inducer for LOX-1 expression and as a new ligand for LOX-1.
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. angela.pirillo@guest.unimi.it
Angela
A
Pirillo
Alice
A
Reduzzi
Nicola
N
Ferri
Hartmut
H
Kuhn
Alberto
A
Corsini
Alberico L
AL
Catapano
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008024:Ligands; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D001093:Arachidonate 15-Lipoxygenase; D048051:p38 Mitogen-Activated Protein Kinases