ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs
J. physiol. biochem
; 73(2): 287-296, mayo 2017. graf, ilus
Artigo
em Inglês
| IBECS
| ID: ibc-168485
Biblioteca responsável:
ES1.1
Localização: BNCS
ABSTRACT
Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway (AU)
RESUMEN
No disponible
Buscar no Google
Coleções:
Bases de dados nacionais
/
Espanha
Base de dados:
IBECS
Assunto principal:
Esfingosina
/
Endotélio Vascular
/
Lisofosfolipídeos
/
Transdução de Sinais
/
Fosfatidilinositol 3-Quinases
/
Receptores de Lisoesfingolipídeo
/
Receptores Depuradores Classe B
Limite:
Humanos
Idioma:
Inglês
Revista:
J. physiol. biochem
Ano de publicação:
2017
Tipo de documento:
Artigo
Instituição/País de afiliação:
Maternal and Child Health Hospital of Hubei Province/China
/
Peking Union Medical College/China
/
The First Affiliated Hospital/China
/
University of South China/China