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Dasatinib suppresses atherosclerotic lesions by suppressing cholesterol uptake in a mouse model of hypercholesterolemia
http://hdl.handle.net/10271/00004269
http://hdl.handle.net/10271/00004269d6997e3b-bc6f-4224-bc7c-41ea72e90171
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (1.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2023-02-15 | |||||||
| タイトル | ||||||||
| タイトル | Dasatinib suppresses atherosclerotic lesions by suppressing cholesterol uptake in a mouse model of hypercholesterolemia | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | Atherosclerosis | |||||||
| キーワード | ||||||||
| 主題 | Cardiovascular event | |||||||
| キーワード | ||||||||
| 主題 | Cd36 | |||||||
| キーワード | ||||||||
| 主題 | Dasatinib | |||||||
| キーワード | ||||||||
| 主題 | Sortilin | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | 高脂血症モデルマウスにおいてダサチニブはコレステロールの取り込みを抑制し動脈硬化病変を抑制する | |||||||
| 著者 |
髙羽, 理光
× 髙羽, 理光
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| 書誌情報 |
en : Journal of Pharmacological Sciences 巻 149, 号 3, p. 158-165, 発行日 2022-07 |
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| 出版者 | ||||||||
| 出版者 | Elsevier | |||||||
| 言語 | en | |||||||
| 出版者 | ||||||||
| 出版者 | 日本薬理学会 | |||||||
| 言語 | ja | |||||||
| 出版者 | ||||||||
| 出版者 | The Japanese Pharmacological Society | |||||||
| 言語 | en | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | Copyright 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Although the use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia is known to cause vascular adverse events (VAEs), the frequency of VAEs during dasatinib administration is not high, and the same holds for atherosclerosis-related VAEs. However, its effect on atherosclerosis remains controversial. In this study, our primary objective was to investigate how dasatinib affects atherosclerosis. Ldlr-/-/Apobec1-/- mice, which are highly prone to develop atherosclerosis, were administered dasatinib. After 16 weeks, we evaluated their atherosclerotic lesions. We used bone-marrow-derived macrophages to investigate the uptake of oxidized low-density lipoprotein (LDL) complexed with DiI dye (DiI-oxLDL). RNA sequencing and quantitative reverse transcription polymerase chain reaction (RTqPCR) were performed to explore the potential effects of dasatinib on cholesterol metabolism. Dasatinib administration significantly reduced atherosclerotic lesions (P<0.001 and P=0.013) and DiI-oxLDL uptake (P<0.001) unlike other TKIs. RNA sequencing and RT-qPCR suggested that Sort1, which encodes sortilin, a known regulator of LDL uptake, and Cd36 were potential targets of dasatinib. In conclusion, dasatinib induced elevated LDL-C levels, but oxLDL uptake in macrophages were suppressed, resulting in reducing atherosclerotic lesions. These results further our understanding of the differences in VAEs between dasatinib and other TKIs. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2022-09-16 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第915号 | |||||||
| ISSN | ||||||||
| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 1347-8613 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1347-8648 | |||||||
| NII書誌ID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA11806667 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 35641028 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1016/j.jphs.2022.04.009 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
