易布鲁替尼诱导的肺血管酶转化酶激活促进大鼠心房动
1Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
iScience
|February 15, 2024
概括
易布鲁替尼因激活血管转化酶 (ACE) 和Src信号通路而引起心房动 (AF). 梨布里尔通过准ACE-Src轴来防止这种AF的发展.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 伊布鲁替尼引起的心房动 (AF) 背后的机制尚未完全理解.
- 易布鲁替尼是布鲁顿的氨酸激酶抑制剂,用于癌症治疗.
研究的目的:
- 为了阐明ibrutinib诱导的AF的分子机制.
- 调查血管素转化酶 (ACE) 和Src信号传递在易布鲁丁尼布诱导的AF中的作用.
- 评估二在预防易布鲁丁尼布诱导的AF方面的潜力.
主要方法:
- 鼠被用ibrutinib治疗了4周,以诱导AF.
- 评估了心房重塑,纤维化和连接素表达.
- 研究了C端 Src 激酶 (CSK) 和 Src 激活.
- 检查了内皮细胞和心房组织中的血管素转化酶 (ACE) 和血管素II (Ang II) 水平.
- 评估了二对易布鲁丁尼布诱导的变化的影响.
主要成果:
- 伊布鲁替尼治疗导致诱导性AF,左心房扩大,纤维化,并降低了素表达在老鼠.
- 这些变化与C端Src激酶 (CSK) 抑制和Src激活相关.
- 易布鲁替尼通过PI3K-AKT通路的抑制增加了ACE蛋白表达和循环Ang II水平,但不是在左心室.
- 二通过抑制ACE激活和下游CSK-Src信号传递,显著降低了心房重塑和AF促进.
结论:
- 易布鲁替尼诱导的AF是由ACE及其下游CSK-Src信号通路的激活介导的.
- ACE激活有助于心房重塑和AF发展.
- 针对ACE-Src途径,使用诸如印布利尔之类的药物,可能为预防易布鲁替尼诱导的AF提供一种策略.
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