%0 Journal Article
%T Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE£¿/£¿ Mice: Shown by Rage Directed Imaging
%A Yared Tekabe
%A Maria Kollaros
%A Qing Li
%A Geping Zhang
%A Chong Li
%A Ann Marie Schmidt
%A Lynne L. Johnson
%J International Journal of Molecular Imaging
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/695391
%X Objective. Receptor for advanced glycated endproducts (RAGE) plays an important role in atherogenesis in diabetes. We imaged RAGE to investigate the effect of glucose control to suppress RAGE and reduce atherosclerosis in apolipoprotein E null (apoE£¿/£¿) diabetic mice. Methods and Results. Thirty-three apoE£¿/£¿ mice received streptozotocin and 6 weeks later 15 began treatment with insulin implants. Blood glucose measurements during study averaged: 140 ¡À 23£¿mg/dL (treated) and 354 ¡À 14£¿mg/dL (untreated). After 15£¿wk 30£¿mice were injected with -anti-RAGE , 3 with -nonimmune IgG , and all with CT contrast agent and underwent SPECT/CT imaging. At necropsy, the proximal aorta was weighed, counted, and sectioned and the % injected dose per gram (%ID/g) was calculated. From the merged SPECT/CT scans, tracer uptake localized to arteries was lower in the treated mice: versus %ID ( ). Percent cross-sectional lesion area was smaller in the treated ( % versus %) ( ). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g ( ; ). Lesion size as percent cross-sectional area was smaller in the treated ( % versus %) ( ). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g ( ; ). Conclusions. These results support the importance of suppressing RAGE to reduce atherosclerotic complications of diabetes and value of molecular imaging to assess treatment effect. 1. Introduction Type I diabetes is associated with increased risk of atherosclerotic macrovascular disease [1, 2]. While nonglycemic risk factors associated with the metabolic syndrome contribute to risk for cardiovascular (CV) events in type II diabetes, hyperglycemia has an independent effect to increase risk [2¨C4]. The nonenzymatic reaction between glucose and proteins known as glycation or glycosylation produces increased levels of glycoxidation products or advanced glycation endproducts (AGEs) in vascular endothelial cells and extracellular space. AGEs as well as other inflammatory ligands interact with a multiligand cell receptor (receptor for advanced glycation endproducts¡ªRAGE) and initiate a positive feedback loop whereby more binding leads to further RAGE upregulation. RAGE and its ligands play a critical role in vascular inflammation, endothelial dysfunction, and atherosclerotic plaque development [5¨C7]. In an autopsy study of coronary arteries from sudden cardiac death subjects, greater RAGE expression was found in coronary atheroma from diabetic compared to nondiabetic subjects [8]. Analysis of carotid plaques
%U http://www.hindawi.com/journals/ijmi/2014/695391/