KMID : 1200020220460030506
|
|
Diabetes & Metabolism Journal 2022 Volume.46 No. 3 p.506 ~ p.511
|
|
GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells
|
|
Kim Joo-Won
Roh Eun Choi Kyung-Mook Yoo Hye-Jin Hwang Hwan-Jin Baik Sei-Hyun
|
|
Abstract
|
|
|
Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-¥êB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-¥êB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.
|
|
KEYWORD
|
|
Cell adhesion molecules, Human umbilical vein endothelial cells, Inflammation, Receptors, G-protein-coupled 40
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|