AIMS: Receptor for advanced glycation end products (RAGE) 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 RAGE deficiency on atherosclerosis in hyperlipidaemic mice. METHODS AND RESULTS: RAGE-/- 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 RAGE 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 RAGE 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 RAGE in the hyperlipidaemic state. RAGE inactivation inhibits the atherosclerosis through reducing oxLDL-induced pro-inflammatory responses and oxidative stress in hyperlipidaemia.
AIMS: Receptor for advanced glycation end products (RAGE) 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 RAGE deficiency on atherosclerosis in hyperlipidaemic mice. METHODS AND RESULTS:RAGE-/- 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 RAGE 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 RAGE 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 RAGE in the hyperlipidaemic state. RAGE inactivation inhibits the atherosclerosis through reducing oxLDL-induced pro-inflammatory responses and oxidative stress in hyperlipidaemia.
Authors: Vladimir R Babaev; Richard R Whitesell; Liying Li; MacRae F Linton; Sergio Fazio; James M May Journal: Free Radic Biol Med Date: 2010-10-23 Impact factor: 7.376
Authors: Sowmya Soman; Rajesh Raju; Varot K Sandhya; Jayshree Advani; Aafaque Ahmad Khan; H C Harsha; T S Keshava Prasad; P R Sudhakaran; Akhilesh Pandey; Puneeth K Adishesha Journal: J Cell Commun Signal Date: 2012-11-19 Impact factor: 5.782
Authors: Sergio Raposeiras-Roubín; Bruno K Rodiño-Janeiro; Beatriz Paradela-Dobarro; Lilian Grigorian-Shamagian; José M García-Acuña; Pablo Aguiar-Souto; Michel Jacquet-Hervet; María V Reino-Maceiras; Ezequiel Alvarez; José R González-Juanatey Journal: Cardiovasc Diabetol Date: 2012-08-21 Impact factor: 9.951