Effect of advanced glycation end products on lectin-like oxidized low density lipoprotein receptor-1 expression in endothelial cells

Aim: lectin-like oxidized ldl receptor-1 (lox-1) is a class e oxidized ldl specific scavenger receptor that recognizes multiple ligands. advanced glycation end products (ages) have been recently identified as other ligands to lox-1 and shown to increase lox-1 expressions in diabetes; therefore,we investigated the underlying mechanism involved. methods: confluent human aortic endothelial cells were treated with a fixed concentration of agebsa or bsa as a control in the presence or absence of either antibody of the receptor for advanced glycation end products,mammalian target of rapamycin (mtor) inhibitor rapamycin,nf-kb inhibitor,phosphoinositide 3-kinases (pi3k) inhibitor or anti-diabetic drug metformin. after stimulation,cells were lysed and western blot protein expression on lox-1,rapamycin-insensitive companion of mtor (rictor),the phosphorylation status of p-mtor,p-p70s6 kinase and p-akt were determined. results: ages induced lox-1 expression in endothelial cells. pretreatment either with anti-rage antibody or ly294002 prior to age-bsa decreases lox-1 and p-mtor expressions. incubating endothelial cells with age-bsa in the presence of rapamycin down-regulated the protein expressionlevel of p-mtor by 41% (p<0.05) and lox-1 expression by 61.5% (p<0.01). knockdown of rictor by rna silencing showed a 41.5% (p<0.01) and 71.2% (p<0.01) reduction in lox-1 and p-akt expressions,respectively. preincubation of endothelial cells with age-bsa and metformin,an anti-diabetic drug known to have an mtor inhibition effect,significantly reduced agestimulated lox-1 expression. conclusion: our results indicated that lox-1 up-regulation induced by age-bsa was a receptor mediated through rage and is via the pi3k/pdk1/mtorc2 pathway. metformincan reduce age-stimulated lox-1 expression in endothelial cells in vitro.