| Item type |
文献 / Documents(1) |
| 公開日 |
2024-05-22 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 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 |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.1016/j.biopha.2023.115504 |
|
|
関連名称 |
10.1016/j.biopha.2023.115504 |
| 出版タイプ |
|
|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
|
|
タイトル |
Angiogenesis inhibitor-specific hypertension increases the risk of developing aortic dissection |
| タイトル別表記 |
|
|
その他のタイトル |
血管新生阻害剤特異的な高血圧は大動脈解離発症のリスクを高める |
| 著者 |
辻󠄀中, 海斗
(井澤)石澤, 有紀
ミヤタ, コウジ
ヨシオカ, トシヒコ
オオミネ, コウヘイ
ニシ, ホノカ
コンドウ, マサテル
イトカズ, シュウト
ミヤタ, タツミ
新村, 貴博
サトウ, マキ
相澤, 風花
八木, 健太
中馬, 真幸
座間味, 義人
合田, 光寛
石澤, 啓介
|
| 抄録 |
|
|
内容記述 |
Aortic dissection is an adverse event of angiogenesis inhibitors; however, the association between the drugs and aortic dissection is unclear. Therefore, we investigated if and how angiogenesis inhibitors increase the onset of aortic dissection using pharmacologically-induced aortic dissection-prone model (LAB) mice, cultured endothelial cells, and real-world databases, which is a novel integrated research approach. Disproportionality analysis was performed and calculated using the reporting odds ratio as a risk signal using a worldwide database of spontaneous adverse events to estimate the risk of adverse events. Angiogenesis inhibitors, but not other hypertension-inducing drugs, showed significant risk signals for aortic aneurysms and dissection. A retrospective cohort analysis using JMDC, a medical receipt database in Japan, showed that the history of atherosclerosis and dyslipidemia, but not hypertension, were significantly associated with the onset of aortic dissection during angiogenesis inhibitor medication administration. For in vivo studies, sunitinib (100 mg/kg/day) was administered to LAB mice. Sunitinib increased systolic blood pressure (182 mmHg vs. 288 mmHg with sunitinib; p＜0.01) and the incidence of aortic dissection (40% vs. 59% with sunitinib; p = 0.34) in mice. In vivo and in vitro studies revealed that sunitinib increased endothelin-1 expression and induced endothelial cell damage evaluated by intracellular- and vascular cell adhesion molecule-1 expressions. The increased risk of developing aortic dissection with angiogenesis inhibitors is associated with the development of drug-specific hypertension via endothelial cell damage and endothelin-1 expression. Our findings are invaluable in establishing safer anticancer therapies and strategies to prevent the development of vascular toxicity in high-risk patients. |
| キーワード |
|
|
主題 |
Angiogenesis inhibitors |
| キーワード |
|
|
主題 |
Aortic dissection |
| キーワード |
|
|
主題 |
Real-world database |
| キーワード |
|
|
主題 |
Hypertension |
| キーワード |
|
|
主題 |
FDA Adverse Event Reporting System |
| 書誌情報 |
en : Biomedicine & Pharmacotherapy
巻 167,
p. 115504,
発行日 2023-09-16
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
07533322 |
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19506007 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10506249 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA11523196 |
| 出版者 |
|
|
出版者 |
Elsevier |
| 備考 |
|
|
値 |
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| EID |
|
|
識別子 |
406562 |
| 言語 |
|
|
言語 |
eng |
| 報告番号 |
|
|
学位授与番号 |
甲第3798号 |
| 学位記番号 |
|
|
値 |
甲医第1606号 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2024-03-22 |
| 学位名 |
|
|
学位名 |
博士（医学） |
| 学位授与機関 |
|
|
|
学位授与機関名 |
徳島大学 |
k3798_abstract.pdf (151 KB)
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