Integrative Transcriptomic-Histological Analysis in Dilated Cardiomyopathy Unveils FGFR1 Inhibition as Anti-Cardiac Fibrotic and Cardioprotective Therapy

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-09-10 DOI:10.1016/j.jacbts.2025.101363

Reo Hata MD , Shunsuke Funakoshi MD, PhD , Takeru Makiyama MD, PhD , Takao Kato MD, PhD , Megumi Narita BS , Yasuko Matsumura MS , Ryoko Hirohata MS , Yuki Naka BS , Kazumi Ida MS , Hiroaki Ito MD , Akihiko Yoshizawa MD, PhD , Yasuhito Nannya MD, PhD , Hironori Haga MD, PhD , Seishi Ogawa MD, PhD , Koh Ono MD, PhD , Takeshi Kimura MD, PhD , Yoshinori Yoshida MD, PhD

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引用次数: 0

Abstract

Cardiac fibrosis drives dysfunction in dilated cardiomyopathy (DCM); yet, effective therapies are limited. This study identifies FGFR1 as a critical target in cardiac fibrosis using transcriptomic and histological analyses of 58 human DCM biopsies. FGFR1 expression correlated with fibrosis severity, and inhibition by AZD4547 reduced fibrosis and improved cardiac function in organoid and murine models. These findings validate FGFR1 inhibition as a promising therapeutic strategy for mitigating fibrosis and improving outcomes in heart failure associated with DCM.

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扩张型心肌病的综合转录组-组织学分析揭示了FGFR1抑制作为抗心脏纤维化和心脏保护治疗

扩张型心肌病（DCM）的心肌纤维化驱动功能障碍；然而，有效的治疗方法有限。本研究通过对58例人类DCM活检的转录组学和组织学分析，确定FGFR1是心脏纤维化的关键靶点。FGFR1表达与纤维化严重程度相关，在类器官和小鼠模型中，AZD4547抑制可减少纤维化并改善心功能。这些研究结果验证了FGFR1抑制是缓解纤维化和改善DCM相关心力衰竭预后的有希望的治疗策略。

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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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.