徳島大学 教育・研究者情報データベース(EDB)

1. (英) Ganbaatar B / (日) GANBAATAR BYAMBASUREN / (読) がんばとる びやんばすれん

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2. 福田 大受

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3. (英) Shinohara M

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4. 八木 秀介([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.地域・家庭医療学])

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5. 楠瀬 賢也

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6. 山田 博胤([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域循環器内科学])

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7. 添木 武([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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8. (英) Hirata KI

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9. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

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(英) Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice

(英) 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. 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. 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). 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.

1. (英) Article.ELocationID: 10.5551/jat.54916

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: Atherosclerosis

4. (英) KeywordList.Keyword: Endothelial function

5. (英) KeywordList.Keyword: Inflammation

6. (英) KeywordList.Keyword: S1P

7. (英) KeywordList.Keyword: S1P2 receptor