Vascular senescence and ageing: a role for the MEOX proteins in promoting endothelial dysfunction.
Can J Physiol Pharmacol
; 95(10): 1067-1077, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28727928
ABSTRACT
In the vascular system, ageing is accompanied by the accrual of senescent cells and is associated with an increased risk of vascular disease. Endothelial cell (EC) dysfunction is a hallmark of vascular disease and is characterized by decreased angiogenic potential, reduced nitric oxide bioavailability, impaired vasodilation, increased production of ROS, and enhanced inflammation. In ECs, the major producer of nitric oxide is the endothelial nitric oxide synthase (eNOS) enzyme that is encoded by the NOS3 gene. NOS3/eNOS function is tightly regulated at both the transcriptional and post-transcriptional levels to maintain normal vascular function. A key transcriptional regulator of eNOS expression is p53, which has been shown to play a central role in mediating cellular senescence and thereby vascular dysfunction. Herein, we show that, in ECs, the MEOX homeodomain transcription factors decrease the expression of genes involved in angiogenesis, repress eNOS expression at the mRNA and protein levels, and increase the expression of p53. These findings support a role for the MEOX proteins in promoting endothelial dysfunction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Vasculares
/
Vasos Sanguíneos
/
Envelhecimento
/
Endotélio Vascular
/
Proteínas de Homeodomínio
/
Hemodinâmica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá