Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.
OBJECTIVE
Carbamylated LDL (cLDL) has been recently shown to have robust proatherogenic effects on human endothelial cells in vitro, suggesting cLDL may have a significant role in atherosclerosis in uremia. The current study was designed to determine which receptors are used by cLDL and thus cause the proatherogenic effects.


RESULTS
In ex vivo or in vitro models as well as in intact animals, administration of cLDL was associated with endothelial internalization of cLDL and subendothelial translocation (transcytosis). In vitro recombinant LOX-1 and SREC-1 receptors showed the greatest cLDL binding. However, pretreatment of the endothelial cells with specific inhibiting antibodies demonstrated that cLDL binds mainly to LOX-1 and CD36 receptors. The transcytosis was dependent on SR-A1, SREC-1, and CD36 receptors whereas LOX-1 receptor was not involved. The cytotoxicity was mediated by several studied scavenger receptors, but cLDL-induced monocyte adhesion depended only on LOX-1. The cLDL-induced synthesis of LOX-1 protein significantly contributed to both cytotoxicity and accelerated monocyte adhesion to endothelial cells.


CONCLUSIONS
Our data suggest that cLDL uses a unique pattern of scavenger receptors. They show that LOX-1 receptor, and partially CD36, SREC-1, and SR-A1 receptors, are essential for the proatherogenic effects of cLDL on human endothelial cells.
Apostolov
Eugene O
EO
Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205, USA.
Shah
Sudhir V
SV
Ray
Debarti
D
Basnakian
Alexei G
AG
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D018955:CD36 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D051116:Receptors, Scavenger / Q000502:physiology*; D051127:Scavenger Receptors, Class E / Q000502:physiology; D051128:Scavenger Receptors, Class F / Q000502:physiology
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; C495138:Olr1 protein, mouse; D051116:Receptors, Scavenger; C495126:SCARF1 protein, human; D051127:Scavenger Receptors, Class E; D051128:Scavenger Receptors, Class F; C039916:carbamyl-LDL
Mol Immunol. 2006 Feb;43(3):255-67
16199262
Ann N Y Acad Sci. 2001 Dec;947:214-22; discussion 222-3
11795269
Thromb Haemost. 1997 Aug;78(2):897-901
9268192
FASEB J. 2005 Nov;19(13):1869-71
16123174
Am J Physiol Renal Physiol. 2004 Jul;287(1):F25-32
15010359
Annu Rev Biochem. 1994;63:601-37
7979249
Nature. 2002 Dec 19-26;420(6917):868-74
12490960
Methods. 2007 Nov;43(3):218-22
17920518
Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1836-46
17158646
Clin Chem. 2005 Apr;51(4):719-28
15684275
Metabolism. 1985 Jan;34(1):10-4
3965857
Cardiovasc Res. 2000 Mar;45(4):874-82
10728413
J Am Soc Nephrol. 2000 Oct;11(10):1819-1825
11004212
Arterioscler Thromb Vasc Biol. 2000 Apr;20(4):1116-22
10764682
Kidney Int. 1992 May;41(5):1175-81
1319520
J Clin Invest. 1983 Apr;71(4):950-9
6300194
Circ Res. 2004 Feb 20;94(3):269-70
14976136
Cell. 2001 Feb 23;104(4):503-16
11239408
Kidney Int. 2005 Jul;68(1):173-8
15954906
Nature. 2000 Sep 14;407(6801):233-41
11001066
Nat Med. 2007 Oct;13(10):1176-84
17828273
Alcohol. 2002 Apr;26(3):163-6
12057777
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):826-32
17255534
Kidney Int Suppl. 2001 Feb;78:S102-7
11168993
Circ Res. 2005 Jul 22;97(2):176-84
15961718
Circulation. 2000 Jun 27;101(25):2889-95
10869259
Eur J Clin Invest. 1994 Feb;24(2):105-13
8206079
Methods Mol Biol. 1999;96:171-6
10098135