doi:10.1155/2012/176162 Research Article Increased Inflammation in Atherosclerotic Lesions of Diabetic Akita-LDLr−/ − Mice Compared to Nondiabetic LDLr−/ − Mice

Copyright © 2012 Daniel Engelbertsen 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. Background. Diabetes is associated with increased cardiovascular disease, but the underlying cellular and molecular mechanisms are poorly understood. One proposed mechanism is that diabetes aggravates atherosclerosis by enhancing plaque inflammation. The Akita mouse has recently been adopted as a relevant model for microvascular complications of diabetes. Here we investigate the development of atherosclerosis and inflammation in vessels of Akitamice on LDLr−/ − background.Methods and Results. Akita-LDLr−/ − and LDLr−/ − mice were fed high-fat diet from 6 to 24 weeks of age. Blood glucose levels were higher in both male and female Akita-LDLr−/ − mice (137 % and 70%, resp.). Male Akita-LDLr−/ − mice had markedly increased plasma cholesterol and triglyceride levels, a three-fold increase in atherosclerosis, and enhanced accumulation of macrophages and T-cells in plaques. In contrast, female Akita-LDLr−/ − mice demonstrated a modest 29 % increase in plasma cholesterol and no significant increase in triglycerides, atherosclerosis, or inflammatory cells in lesions. Male Akita-LDLr−/ − mice had increased levels of plasma IL-1β compared to nondiabetic mice, whereas no such difference was seen between female diabetic and nondiabetic mice. Conclusion. Akita-LDLr−/ − mice display considerable gender differences in the development of diabetic atherosclerosis. In addition, th