徳島大学 教育・研究者情報データベース(EDB)

1. (英) Rahadian Arief / (日) Arief Rahadian / (読) ありえふ らはでぃあん

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2. 福田 大受

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3. (英) Salim HM

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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.連携研究部門(医学域).寄附講座系(医学域).地域医療人材育成(医学域)])

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5. 楠瀬 賢也([徳島大学.病院.診療科.内科.循環器内科])

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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. 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) Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice

(英) Recent studies have demonstrated that selective sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. Canagliflozin decreased blood glucose (P<0.001) and total cholesterol (P<0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P<0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P<0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P<0.05, both). Methylglyoxal also decreased the phosphorylation of eNOS and Akt but increased the phosphorylation of eNOS and p38 MAPK in HUVECs. Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.

1. 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])

1. (英) Article.ELocationID: 10.5551/jat.52100

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

3. (英) KeywordList.Keyword: Atherosclerosis

4. (英) KeywordList.Keyword: Canagliflozin

5. (英) KeywordList.Keyword: Endothelial dysfunction

6. (英) KeywordList.Keyword: SGLT2 inhibitor