Table of Contents
International Journal of Molecular Imaging
Volume 2014, Article ID 695391, 8 pages
http://dx.doi.org/10.1155/2014/695391
Research Article

Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE−/− Mice: Shown by Rage Directed Imaging

1Department of Medicine, Columbia University Medical Center, 650 West 168 Street, New York, NY 10032, USA
2Department of Medicine, New York University Medical Center, New York, NY 10016, USA

Received 17 January 2014; Accepted 14 March 2014; Published 14 April 2014

Academic Editor: Hideo Saji

Copyright © 2014 Yared Tekabe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 ± 23 mg/dL (treated) and 354 ± 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.