The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells.
Cross talks between the vascular and immune system play a critical role in vascular diseases, in particular in atherosclerosis. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation. Whether OSCAR plays a role in vascular biology and has an impact on atherogenic processes provoked by proinflammatory stimuli is yet unknown. We identified OSCAR on the surface of human primary endothelial cells. Stimulation of endothelial cells with oxidized low-density lipoprotein (oxLDL) caused a time- and dose-dependent induction of OSCAR, which was lectin-like oxidized LDL receptor 1 and Ca(2+) dependent. OSCAR was transcriptionally regulated by oxLDL as shown by OSCAR promoter analysis. Specific inhibition of the nuclear factor of activated T cells (NFAT) pathway prevented the oxLDL-mediated increase of endothelial OSCAR expression. As assessed by EMSA, oxLDL induced binding of NFATc1 to the OSCAR promoter. Notably, in vivo-modified LDL from patients with diabetes mellitus stimulated OSCAR mRNA expression in human endothelial cells. Furthermore, apolipoprotein E knockout mice fed a high-fat diet showed an enhanced aortic OSCAR expression associated with increased expression of NFATc1. In summary, OSCAR is expressed in vascular endothelial cells and is regulated by oxLDL involving NFATc1. Our data suggest that OSCAR, originally described in bone as immunological mediator and regulator of osteoclast differentiation, may be involved in cell activation and inflammation during atherosclerosis.
Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technical University Medical Center, Fetscherstrasse 74, D-01307 Dresden, Germany.
Claudia
C
Goettsch
Martina
M
Rauner
Kathrin
K
Sinningen
Susann
S
Helas
Nadia
N
Al-Fakhri
Katharina
K
Nemeth
Christine
C
Hamann
Steffi
S
Kopprasch
Elena
E
Aikawa
Stefan R
SR
Bornstein
Michael
M
Schoppet
Lorenz C
LC
Hofbauer
D000818:Animals; D050197:Atherosclerosis / Q000473:pathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008077:Lipoproteins, LDL / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
D008077:Lipoproteins, LDL; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C512828:OSCAR protein, human; D011956:Receptors, Cell Surface; C099252:oxidized low density lipoprotein