Dynamic changes in regulatory T cells are linked to levels of diet-induced hypercholesterolemia.
Circulation
; 124(2): 185-95, 2011 Jul 12.
Article
em En
| MEDLINE
| ID: mdl-21690490
ABSTRACT
BACKGROUND:
Regulatory T cells (Treg) are present in atherosclerotic lesions and can modulate disease. In this study we characterized changes in Treg responses associated with prolonged hypercholesterolemia and lesion progression. METHODS ANDRESULTS:
Low-density lipoprotein receptor null mice in which Treg express green fluorescent protein were fed a control or cholesterol-rich diet, and green fluorescent protein-positive cells were enumerated in lymphoid tissues and in aorta. Splenic Treg numbers increased after 4, 8, and 20 weeks in cholesterol-diet-fed mice. However, the number of circulating and lesional Treg peaked at 4 weeks and decreased significantly at 8 and 20 weeks, concomitant with increased numbers of CD4(+) effector T cells and increased lesion size over this period. Treg expression of selectin ligands and their ability to bind to aortic endothelium decreased after prolonged hypercholesterolemia, and apoptosis of lesional Treg increased. After 4 weeks of cholesterol-rich diet, a switch to a control diet for 4 weeks reduced serum cholesterol and stopped lesion growth, and the high aortic Treg content was maintained, compared with mice fed a cholesterol diet for 8 weeks. After the diet reversal, the splenic Treg retained the phenotype of Treg after 4 weeks of cholesterol diet.CONCLUSIONS:
Prolonged hypercholesterolemia impairs Treg but not effector T cell accumulation in lesions, but reversal of hypercholesterolemia can prevent loss of lesional Treg. Therefore, cholesterol-lowering therapies may induce dynamic and beneficial changes in Tregeffector T cell ratios in atherosclerotic lesions.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
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Colesterol na Dieta
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Colesterol
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Linfócitos T Reguladores
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Dieta Aterogênica
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Hipercolesterolemia
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article