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Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation

Cited 20 time in Web of Science Cited 20 time in Scopus
Authors
Ku, Yun Hyi; Cho, Bong-Jun; Kim, Min Joo; Lim, Soo; Park, Young Joo; Jang, Hak C.; Choi, Sung Hee
Issue Date
2017-08-30
Publisher
BioMed Central
Citation
BMC Pharmacology and Toxicology, 18(1):62
Keywords
ThiazolidinedionesRosiglitazoneEndothelial cellsVascular permeabilityEdemaAkt
Abstract
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)β. 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.
ISSN
2050-6511
Language
English
URI
https://hdl.handle.net/10371/138317
DOI
https://doi.org/10.1186/s40360-017-0169-y
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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