Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation.
BMC Pharmacol Toxicol
; 18(1): 62, 2017 08 30.
Article
en En
| MEDLINE
| ID: mdl-28854981
ABSTRACT
BACKGROUND:
Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, exhibit anti-inflammatory and antioxidant properties and inhibit endothelial inflammation and dysfunction, which is anti-atherogenic. However, fluid retention, which may lead to congestive heart failure and peripheral edema, is also a concern, which may result from endothelial cell leakage. In the current study, we examined the effects of PPAR-γ agonists on vascular endothelial cell migration and permeability in order to determine its underlying mechanisms.METHODS:
We used rosiglitazone and conducted cell migration assay and permeability assay using HUVEC cells and measured vascular permeability and leakage in male C57BL/6 mice.RESULTS:
Rosiglitazone significantly promoted endothelial cell migration and induced permeability via activation of phosphatidylinositol-3-kinase (PI3K) - Akt or protein kinase C (PKC)ß. In addition, rosiglitazone increased vascular endothelial growth factor (VEGF) expression and suppressed expression of tight junction proteins (JAM-A and ZO-1), which might promote neovascularization and vascular leakage. These phenomena were reduced by Akt inhibition.CONCLUSIONS:
Vascular endothelial cell migration and permeability change through Akt phosphorylation might be a mechanism of induced fluid retention and peripheral tissue edema by TZD.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Permeabilidad Capilar
/
Tiazolidinedionas
/
Proteínas Proto-Oncogénicas c-akt
/
Células Endoteliales de la Vena Umbilical Humana
/
Hipoglucemiantes
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
BMC Pharmacol Toxicol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Corea del Sur