TRα protects against atherosclerosis in male mice: identification of a novel anti-inflammatory property for TRα in mice.
Endocrinology
; 155(7): 2735-45, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24797634
ABSTRACT
Hypothyroidism is associated with an increased occurrence of atherosclerosis, suggesting some protective role for thyroid hormones (THs). Hypercholesterolemia is one of the major risk factor to develop this disease. Here, we show that the well-known TH cholesterol lowering effect was dependent on TH nuclear receptor (TR)ß liver activity. But most importantly, TRα was also shown to contribute of slowing down atherosclerosis progression via an independent mechanism. Introduction of TRα(0/0) deletion in the ApoE(-/-) background accelerated the appearance of plaques. Earlier cholesterol accumulation was detected in aorta macrophages, likely due to impaired cholesterol efflux. The IL-1ß inflammatory cytokine was elevated in serum and macrophages in correlation with an activation of the AKT/nuclear factor κB pathway in these cells. Inhibition of AKT prevented inflammation and restored normal cholesterol efflux. Similar low-grade inflammation was identified in TRα(0/0) male mice. Thus, the mere absence of TRα is associated with elevated levels of cytokines likely responsible for cholesterol accumulation and atherosclerosis. This TRα protective activity should be relevant for other inflammatory pathologies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores alfa dos Hormônios Tireóideos
/
Aterosclerose
/
Inflamação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Endocrinology
Ano de publicação:
2014
Tipo de documento:
Article