TY - JOUR
T1 - GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells
AU - Kim, Joo Won
AU - Roh, Eun
AU - Choi, Kyung Mook
AU - Yoo, Hye Jin
AU - Hwang, Hwan Jin
AU - Baik, Sei Hyun
N1 - Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), South Korea, funded by the Ministry of Education (NRF-2020R1I1A1A01072592 and NRF-2021R1A2C2008792).
Publisher Copyright:
Copyright © 2022 Korean Diabetes Association
PY - 2022/5
Y1 - 2022/5
N2 - 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-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB 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.
AB - 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-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB 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.
KW - Cell adhesion molecules
KW - G-protein-coupled 40
KW - Human umbilical vein endothelial cells
KW - Inflammation; Receptors
UR - http://www.scopus.com/inward/record.url?scp=85131270429&partnerID=8YFLogxK
U2 - 10.4093/dmj.2021.0092
DO - 10.4093/dmj.2021.0092
M3 - Article
C2 - 35067013
AN - SCOPUS:85131270429
SN - 2233-6079
VL - 46
SP - 506
EP - 511
JO - Diabetes and Metabolism Journal
JF - Diabetes and Metabolism Journal
IS - 3
ER -
