局灶黏附激酶驱动Rho/ROCK和mTOR信号保护和增强主动脉夹层

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-08-05 DOI:10.1016/j.jacbts.2025.101353

Zhen Zhou MD , Pujun Guan PhD , Ripon Sarkar PhD , Yang Yu MD , Alexis Richard PhD , Dar Weiss PhD , Yuki Kawamura PhD , Chen Zhang MD , Yanming Li PhD , Tomas Vaisar PhD , Daniel R. Martin PhD , L. Maximillian Buja MD , Zhouxuan Li PhD , Kartik Venkatachalam PhD , Ying H. Shen MD, PhD , Scott A. LeMaire MD , Jay D. Humphrey PhD , Dianna M. Milewicz MD, PhD

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引用次数: 0

摘要

在β-氨基丙腈小鼠模型中，通过局灶粘连（FAs）产生的机械传感功能失调，通过触发FA激酶激活和随后的Rho/ROCK和mTOR信号通路，显著促进胸主动脉夹层的形成。目前的研究结果表明，这些信号通路在上行和下行解剖中起着不同的作用。具体来说，在升主动脉中，平滑肌细胞FA激酶- rho /ROCK信号是一种有益的适应性机制，可防止夹层发生，而mTOR信号则具有致病性，有助于夹层发生。

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Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections

Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase–Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.