number of access : ?
number of downloads : ?
ID 116449
Title Alternative
The Role of S1P2 in Atherogenesis
Author
Ganbaatar, Byambasuren Tokushima University
Shinohara, Masakazu Kobe University
Hirata, Ken-ichi Kobe University
Keywords
Atherosclerosis
Inflammation
Endothelial function
S1P2 receptor
S1P
Content Type
Journal Article
Description
Aim: The bioactive lipid, sphingosine-1-phosphate (S1P), has various roles in the physiology and pathophysiology of many diseases. There are five S1P receptors; however, the role of each S1P receptor in atherogenesis is still obscure. Here we investigated the contribution of S1P receptor 2 (S1P2) to atherogenesis by using a specific S1P2 antagonist, ONO-5430514, in apolipoprotein E-deficient (Apoe−/− ) mice.
Methods: Apoe−/− mice fed with a western-type diet (WTD) received ONO-5430514 (30 mg/kg/day) or vehicle. To examine the effect on atherogenesis, Sudan IV staining, histological analysis, qPCR, and vascular reactivity assay was performed. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments.
Results: WTD-fed Apoe−/− mice had significantly higher S1P2 expression in the aorta compared with wild-type mice. S1P2 antagonist treatment for 20 weeks reduced atherosclerotic lesion development (p<0.05). S1P2 antagonist treatment for 8 weeks ameliorated endothelial dysfunction (p<0.05) accompanied with significant reduction of lipid deposition, macrophage accumulation, and inflammatory molecule expression in the aorta compared with vehicle. S1P2 antagonist attenuated the phosphorylation of JNK in the abdominal aorta compared with vehicle (p<0.05). In HUVEC, S1P promoted inflammatory molecule expression such as MCP-1 and VCAM-1 (p<0.001), which was attenuated by S1P2 antagonist or a JNK inhibitor (p<0.01). S1P2 antagonist also inhibited S1P-induced JNK phosphorylation in HUVEC (p<0.05).
Conclusions: Our results suggested that an S1P2 antagonist attenuates endothelial dysfunction and prevents atherogenesis. S1P2, which promotes inflammatory activation of endothelial cells, might be a therapeutic target for atherosclerosis.
Journal Title
Journal of Atherosclerosis and Thrombosis
ISSN
18803873
13403478
Publisher
Japan Atherosclerosis Society
Volume
28
Issue
6
Start Page
630
End Page
642
Published Date
2021-06-01
Rights
This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License(https://creativecommons.org/licenses/by-nc-sa/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences
University Hospital