Table of Contents
ISRN Pharmacology
Volume 2013 (2013), Article ID 847310, 8 pages
Research Article

Inhibition of Endoplasmic Reticulum Stress and Atherosclerosis by 2-Aminopurine in Apolipoprotein E-Deficient Mice

1Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA
2The Central Hospital of Wuhan, Wuhan 430014, China
3Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Received 28 May 2013; Accepted 8 July 2013

Academic Editors: H. Cerecetto, K. Lutfy, and K. Wada

Copyright © 2013 Lichun Zhou 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.


We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout ( ) mice, so called E/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2α (eIF-2α). Furthermore, the eIF-2α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control mice. In addition, the 2-AP-treated mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2α in their aortic samples as compared to levels in untreated control mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in mice and that therapeutic strategies can be developed for using eIF-2α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis.