药理和基因抑制BTK可改善血管变性、剥离和破裂

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-03-04 DOI:10.1016/j.lfs.2025.123533

Songwen Li , Gang Liu , Shuo Cheng , Xin Li , Xinyu Weng , Jing Yang

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引用次数: 0

摘要

主动脉动脉瘤和夹层（AAD）涉及复杂的免疫反应，巨噬细胞在血管炎症和AAD进展中起核心作用。本研究的目的是确定布鲁顿酪氨酸激酶（BTK）在巨噬细胞介导的炎症中的作用及其对AAD进展的影响。主要方法采用药理学和遗传学方法抑制β-氨基丙腈（BAPN）和血管紧张素II （Ang II）诱导的AAD模型中的BTK，通过组织学分析、RNA测序和分子分析评估巨噬细胞极化、炎症反应和AAD的进展。主要发现sbtk在主动脉夹层手术患者和AAD小鼠模型的主动脉组织中均上调。BTK抑制显著减少巨噬细胞浸润，调节巨噬细胞极化，并通过限制血管炎症减轻AAD的进展。这些发现表明BTK是巨噬细胞驱动的血管炎症的关键调节因子，也是AAD的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Pharmacological and genetic inhibition of BTK ameliorates vascular degeneration, dissection, and rupture

Aims

Aortic aneurysm and dissection (AAD) involves complex immune responses, with macrophages playing a central role in vascular inflammation and AAD progression. The aim of this study was to determine the role of Bruton's tyrosine kinase (BTK) in macrophage-mediated inflammation and its impact on AAD progression.

Main methods

We employed pharmacological and genetic approaches to inhibit BTK in AAD models induced by β-aminopropionitrile (BAPN) and angiotensin II (Ang II). Histological analysis, RNA sequencing, and molecular assays were used to assess macrophage polarization, inflammatory responses and progression of AAD.

Key findings

BTK was upregulated in both aortic tissue from patients undergoing surgery for aortic dissection and AAD mice model. BTK inhibition significantly reduced macrophage infiltration, modulated macrophage polarization, and attenuated AAD progression by limiting vascular inflammation.

Significance

These findings establish BTK as a key regulator of macrophage-driven vascular inflammation and a promising therapeutic target for AAD.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.