[Relationship between accelerated artherosclerosis and Treg/Teff balance in uremic apoE-/- mice].
OBJECTIVE
To establish a uremic apolipoprotein E knockout (apoE-/-) mouse model and explore the relationship between accelerated atherosclerosis and Treg/Teff balance.


METHODS
Using apoE-/- mice with C57BL/6J background, uremic apoE-/- mice were created by electrocautery of the right kidney and nephrectomy of the left, and the control apoE-/- mice received a sham-operation. Two weeks after inducing uremia, the renal function of the mice were evaluated to assess the validity of the model. Ten weeks after the operation, blood samples were obtained from the mice to assess the renal function and serum total cholesterol (TCH); the serum concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interferon-gamma (IFN-gamma) were detected by ELISA, and CD4(+)CD25(+)Foxp3(+)Treg ratio in the spleen was determined by flow cytometry. RT-PCR was used to detect the expression of Foxp3 and IFN-gamma mRNA in the aorta, and oil red O staining used to investigate the relative atherosclerotic area on the frozen sections of the aortic root. The correlation between the renal function parameters and Treg quantity was analyzed.


RESULTS
Renal function detection confirmed successful establishment of the uremic apoE-/- mouse model. Ten weeks after the operation, the relative atherosclerotic plaque area in the aortic root plaque increased significantly, the spleen Treg ratio decreased, the serum concentrations of TGF-beta(1) decreased and IFN-gamma and TCH increased, the expression of aortic Foxp3 mRNA decreased and IFN-gamma mRNA increased as compared with those in the control apoE-/- mice. A significant inverse correlation was found between the renal function parameters and Treg quantity in uremic apoE-/- mice.


CONCLUSIONS
In uremic apoE-/- mice, accelerated aortic atherosclerosis is correlated to the T cell subset (Treg/Teff) imbalance shown by decreased quantity and impaired function of Treg and enhanced activity of Teff.
Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an 710061, China. shenyan@sogou.com
Yan
Y
Shen
Zu-yi
ZY
Yuan
Yan
Y
Liu
Yan
Y
Xiao
Yue
Y
Wu
Yan
Y
Zhao
Yu-ling
YL
Tian
Wei-min
WM
Liu
Li-jun
LJ
Wang
Xiao
X
Liang
Tao
T
Chen
Tao
T
Geng
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055786:Gene Knockout Techniques; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D011897:Random Allocation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014511:Uremia / Q000150:complications / Q000235:genetics* / Q000276:immunology*
D001057:Apolipoproteins E; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D002784:Cholesterol