{"created":"2024-11-22T07:49:00.665257+00:00","id":2008849,"links":{},"metadata":{"_buckets":{"deposit":"3fd27d00-e712-40b4-85b5-20585c900f7a"},"_deposit":{"created_by":7,"id":"2008849","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2008849"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02008849","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["183","231","197","564","340","309"],"control_number":"2008849","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_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","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"Canagliflozin and Vascular Function","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-11-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"11","bibliographicPageEnd":"1151","bibliographicPageStart":"1141","bibliographicVolumeNumber":"27","bibliographic_titles":[{"bibliographic_title":"Journal of Atherosclerosis and Thrombosis","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.\nMethod: 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.\nResult: 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.\nConclusion: 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.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Japan Atherosclerosis Society","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"18803873","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"13403478","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3494号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-23"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は，著者Arief Rahadianの学位論文として提出され，学位審査・授与の対象となっている。\n学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1476号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.5551/jat.52100"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.5551/jat.52100","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"366058"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ラハディアン, 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inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Canagliflozin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Atherosclerosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Endothelial dysfunction","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1716268551628"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-06-15"},"publish_date":"2021-06-15","publish_status":"0","recid":"2008849","relation_version_is_last":true,"title":["Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2025-02-10T06:42:02.576438+00:00"}