We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis in non-diabetic LDL receptor-deficient mice.
- Authors
Li Sun; Tatsuro Ishida; Tomoyuki Yasuda; Yoko Kojima; Tomoyuki Honjo; Yasuhiko Yamamoto; Hiroshi Yamamoto; Shun Ishibashi; Ken-ichi Hirata; Yoshitake Hayashi
- Abstract
: 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.
- Subjects
LOW density lipoproteins; INFLAMMATION; ATHEROSCLEROSIS; DIABETIC angiopathies; VASCULAR diseases; LABORATORY mice; OXIDATIVE stress; GENETICS
- Publication
Cardiovascular Research, 2009, Vol 82, Issue 2, p371
- ISSN
0008-6363
- Publication type
Article