Dataset Information

Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.

ABSTRACT: 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.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.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.

SUBMITTER: Apostolov EO

PROVIDER: S-EPMC5075391 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.

Apostolov Eugene O EO Shah Sudhir V SV Ray Debarti D Basnakian Alexei G AG

Arteriosclerosis, thrombosis, and vascular biology 20090820 10

<h4>Objective</h4>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.<h4>Methods and results</h4>In ex vivo or in vitro models as well as in intact animals, administration of cLDL was associated with endothelial internalization of cLDL ...[more]

PMID: 19696406

Similar Datasets

Project description:Endocytosis of formaldehyde-treated serum albumin (FSA) mediated by the scavenger receptor was studied in rat liver endothelial cells. Suspended cells had about 8000 receptors/cell, whereas cultured cells had about 19,000 receptors/cell. Kd was 10(-8) M in both systems. Cell-surface scavenger receptors were found exclusively in coated pits by electron microscopy, by using ligand labelled with colloidal gold. Cell-surface-bound FSA could be released by decreasing the pH to 6.0; it was therefore possible to assess the rate of internalization of surface-bound ligand. This rate was very high: t1/2 for internalization of ligand prebound at 4 degrees C was 24 s. The endocytic rate constant at 37 degrees C, Ke, measured as described by Wiley & Cunningham [(1982) J. Biol. Chem. 257, 4222-4229], was 2.44 min-1, corresponding to t1/2 = 12 s. Uptake of FSA at 37 degrees C after destruction of one cell-surface pool of receptors by Pronase was decreased to 60%. This finding is compatible with a relatively large intracellular pool of receptors. The intracellular handling of 125I-tyramine-cellobiose-labelled FSA (125I-TC-FSA) was studied by subcellular fractionation in sucrose gradients, Nycodenz gradients or by differential centrifugation. The density distributions of degraded and undegraded 125I-TC-FSA after fractionation of isolated non-parenchymal cells and whole liver were similar, when studied in Nycodenz and sucrose gradients, suggesting that the subcellular distribution of the ligand was not influenced by the huge excess of non-endothelial material in a whole liver homogenate. Fractionation in sucrose gradients showed that the ligand was sequentially associated with organelles banding at 1.14, 1.17 and 1.21 g/ml. At 9-12 min after intravenous injection the ligand was in a degradative compartment, as indicated by the accumulation of acid-soluble radioactivity at 1.21 g/ml. A rapid transfer of ligand to the lysosomes was also indicated by the finding that a substantial proportion of the ligand could be degraded by incubating mitochondrial fractions prepared 12 min after intravenous injection of the ligand. The results indicate that FSA is very rapidly internalized and transferred through an endosomal compartment to the lysosomes. The endosomes are gradually converted into lysosomes between 9 and 12 min after injection of FSA. The rate-limiting step in the intracellular handling of 125I-TC-FSA is the degradation in the lysosomes.

Project description:1. Hepatic uptake of low-density lipoprotein (LDL) in parenchymal cells and non-parenchymal cells was studied in control-fed and cholesterol-fed rabbits after intravenous injection of radioiodinated native LDL (125I-TC-LDL) and methylated LDL (131I-TC-MetLDL). 2. LDL was taken up by rabbit liver parenchymal cells, as well as by endothelial and Kupffer cells. Parenchymal cells, however, were responsible for 92% of the hepatic LDL uptake. 3. Of LDL in the hepatocytes, 89% was taken up via the B,E receptor, whereas 16% and 32% of the uptake of LDL in liver endothelial cells and Kupffer cells, respectively, was B,E receptor-dependent. 4. Cholesterol feeding markedly reduced B,E receptor-mediated uptake of LDL in parenchymal liver cells and in Kupffer cells, to 19% and 29% of controls, respectively. Total uptake of LDL in liver endothelial cells was increased about 2-fold. This increased uptake is probably mediated via the scavenger receptor. The B,E receptor-independent association of LDL with parenchymal cells was not affected by the cholesterol feeding. 5. It is concluded that the B,E receptor is located in parenchymal as well as in the non-parenchymal rabbit liver cells, and that this receptor is down-regulated by cholesterol feeding. Parenchymal cells are the main site of hepatic uptake of LDL, both under normal conditions and when the number of B,E receptors is down-regulated by cholesterol feeding. In addition, LDL is taken up by B,E receptor-independent mechanism(s) in rabbit liver parenchymal, endothelial and Kupffer cells. The non-parenchymal liver cells may play a quantitatively important role when the concentration of circulating LDL is maintained at a high level in plasma, being responsible for 26% of hepatic uptake of LDL in cholesterol-fed rabbits as compared with 8% in control-fed rabbits. The proportion of hepatic LDL uptake in endothelial cells was greater than 5-fold higher in the diet-induced hypercholesterolaemic rabbits than in controls.

Dataset Information

Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.

Publications

Scavenger receptors of endothelial cells mediate the uptake and cellular proatherogenic effects of carbamylated LDL.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure