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Increased Inflammation in Atherosclerotic Lesions of Diabetic Akita-LDLr(-/-) Mice Compared to Nondiabetic LDLr(-/-) Mice.

Engelbertsen, Daniel LU ; To, Fong LU ; Dunér, Pontus LU ; Kotova, Olga LU ; Söderberg, Ingrid LU ; Alm, Ragnar LU ; Gomez, Maria LU ; Nilsson, Jan LU and Bengtsson, Eva LU (2012) In Experimental Diabetes Research 2012(Nov.,28).
Abstract
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 Akita mice 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... (More)
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 Akita mice 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, the increased atherosclerosis in male Akita-LDLr(-/-) mice is associated with an increase in inflammatory cells in lesions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Diabetes Research
volume
2012
issue
Nov.,28
publisher
Hindawi Publishing Corporation
external identifiers
  • wos:000312013600001
  • pmid:23243415
  • scopus:84871406504
ISSN
1687-5214
DOI
10.1155/2012/176162
language
English
LU publication?
yes
id
99e6f8de-398e-4515-9614-15d51e53dd2e (old id 3347158)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23243415?dopt=Abstract
date added to LUP
2013-01-02 16:55:13
date last changed
2017-09-10 03:27:33
@article{99e6f8de-398e-4515-9614-15d51e53dd2e,
  abstract     = {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 Akita mice 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, the increased atherosclerosis in male Akita-LDLr(-/-) mice is associated with an increase in inflammatory cells in lesions.},
  articleno    = {176162},
  author       = {Engelbertsen, Daniel and To, Fong and Dunér, Pontus and Kotova, Olga and Söderberg, Ingrid and Alm, Ragnar and Gomez, Maria and Nilsson, Jan and Bengtsson, Eva},
  issn         = {1687-5214},
  language     = {eng},
  number       = {Nov.,28},
  publisher    = {Hindawi Publishing Corporation},
  series       = {Experimental Diabetes Research},
  title        = {Increased Inflammation in Atherosclerotic Lesions of Diabetic Akita-LDLr(-/-) Mice Compared to Nondiabetic LDLr(-/-) Mice.},
  url          = {http://dx.doi.org/10.1155/2012/176162},
  volume       = {2012},
  year         = {2012},
}