Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice 11

• Material Type: 博士論文
• ISSN: 1880-3873
• Title: Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice
• Volume: 27 11
• Author/Editor: Rahadian, Arief; Fukuda, Daiju; Salim, Hotimah Masdan; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• Author Heading: Rahadian, Arief; Fukuda, Daiju; Salim, Hotimah Masdan; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• Publication, Distribution, etc.: Japan Atherosclerosis Society
• Publication Date: 2020-11-01
• Publication Date (W3CDTF): 2020-11-01
• Alternative Title: カナグリフロジンは、ApoE欠損マウスの糖尿病誘発性血管機能障害を予防する; Canagliflozin and Vascular Function
• Periodical title: Journal of Atherosclerosis and Thrombosis
• Degree grantor/type: 徳島大学
• Date Granted: 2021-03-23
• Date Granted (W3CDTF): 2021-03-23
• Dissertation Number: 甲第3494号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3494号
• Text Language Code: eng
• Subject Heading: SGLT2 inhibitor; Canagliflozin; Atherosclerosis; Endothelial dysfunction
• Target Audience: 一般
• Note (General): Aim: 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.Method: 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.Result: 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 eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs.Conclusion: 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.
• DOI: info:doi/10.5551/jat.52100; https://doi.org/info:doi/10.5551/jat.52100
• Persistent ID (NDL): info:ndljp/pid/11692590; https://dl.ndl.go.jp/pid/11692590
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-07-05T22:24:43+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115926
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp