RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis in non-diabetic LDL receptor-deficient mice.

AIMS:Receptor for advanced glycation end products plays a pivotal role in the genesis of diabetic vascular diseases. To further explore the mechanisms underlying atherosclerosis under non-diabetic conditions, we examined the effect of deficiency on atherosclerosis in hyperlipidaemic mice. METHODS AND mice were crossed with low-density lipoprotein receptor-deficient (LDLr-/-) mice to generate the double knockout (DKO) mice. After feeding with high-fat diet for 12 weeks, aortic atherosclerotic lesions were analysed histologically in these mice. Although there were no differences in serum levels of glucose and known duanyu1648 ligands between DKO and LDLr-/- mice, DKO mice exhibited a significant decrease in the size and macrophage content in atherosclerotic lesions compared with LDLr-/- mice. Expression of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the aorta was lower in DKO mice than in LDLr-/- mice. Fluorescence-based assays revealed that oxidative stress in the vessel wall was attenuated in DKO mice than in LDLr-/- mice. Cell culture experiments revealed that duanyu1648 mediated oxidative LDL-induced activation of p42/44 mitogen-activated protein kinases and oxidative stress in macrophages. CONCLUSION:Oxidative LDL may be a ligand of duanyu1648 in the hyperlipidaemic state. duanyu1648 inactivation inhibits the atherosclerosis through reducing oxLDL-induced pro-inflammatory responses and oxidative stress in hyperlipidaemia.

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