Advanced Glycation End-Products Downregulate HoxA9EC through Activation of Nuclear Factor Kappa B by Reciprocal Interaction.
J Vasc Res
; 54(4): 226-234, 2017.
Article
em En
| MEDLINE
| ID: mdl-28723696
ABSTRACT
Advanced glycation end-products (AGEs) have been recognized as an important pathophysiological mechanism in endothelial dysfunction during diabetic atherogenesis. Homeobox (Hox) genes have been identified as playing a regulatory role in the adult cardiovascular system. Regulation of HoxA9EC is involved in diabetic endothelial dysfunction, but the mechanism of HoxA9EC regulation has remained undefined. Here, we sought to investigate how HoxA9EC is regulated in AGE-induced endothelial dysfunction and to explore the mechanism involved. We used human umbilical venous endothelial cells (HUVECs) cocultured with AGEs, and examined endothelial nitric oxide synthase (eNOS) activation, nitric oxide (NO) release, cell migration, and the expression of HoxA9EC and nuclear factor kappa B (NF-κB). AGEs suppressed eNOS activation, NO release, and the migration of HUVECs. Knockout of HoxA9EC also reduced eNOS activation, NO release, and the migration of HUVECs, and the enhancement of HoxA9EC improved the function of HUVECs. Furthermore, AGEs downregulated HoxA9EC expression and activated NF-κB, and the depression of HoxA9EC was significantly attenuated by the NF-κB inhibitor. On the other hand, knockout of HoxA9EC activated NF-κB and the enhancement of HoxA9EC suppressed NF-κB activation. In conclusion, AGEs could induce endothelial dysfunction through NF-κB-dependent HoxA9EC downregulation by reciprocal interaction, and the enhancement of HoxA9EC expression could attenuate the impairment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Produtos Finais de Glicação Avançada
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Proteínas de Homeodomínio
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Células Endoteliais da Veia Umbilical Humana
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Vasc Res
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China