Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.
Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.
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DOI:
10.1161/atvbaha.109.189795
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发表时间:
2009-10
期刊:
影响因子:
--
通讯作者:
Basnakian AG
中科院分区:
文献类型:
--
作者:
Apostolov EO;Shah SV;Ray D;Basnakian AG
Carbamylated LDL (cLDL) has been recently shown to have robust pro-atherogenic effects upon 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 so may cause the pro-atherogenic effects. 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 while 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. Our data suggest that cLDL utilizes unique pattern of scavenger receptors. They show that LOX-1 receptor, and partially, CD36, SREC-1 and SR-A1 receptors are essential for the pro-atherogenic effects of cLDL on human endothelial cells.