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REVIEW article

Front. Immunol.

Sec. Comparative Immunology

TWEAK-Fn14: A promising target for cardio-cerebrovascular diseases and brain-heart syndrome

Provisionally accepted
Qinglin FeiQinglin Fei1Chang JunChang Jun2Tingcan JiangTingcan Jiang1Guoqiang GuanGuoqiang Guan1Yujuan LiangYujuan Liang1Cuicui ChengCuicui Cheng1Guangxu XiaoGuangxu Xiao1Qiuyan GuoQiuyan Guo3Guanwei FanGuanwei Fan2Yan ZhuYan Zhu1Ming LyuMing Lyu1*
  • 1State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • 3State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

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Abstract: Cardio-cerebrovascular diseases (CCVDs), notably stroke and coronary heart disease, represent the leading causes of mortality and disability worldwide. The intricate bidirectional feedback between the brain and heart in brain-heart syndrome (BHS) exacerbates clinical outcomes and imposes a significant economic burden on patients. The cytokine tumor necrosis factor-like apoptosis weak inducer (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are overexpressed in cerebral injury and cardiac dysfunction. Elevated levels of TWEAK and Fn14 contribute to the development of various brain diseases, including blood-brain barrier damage, brain edema, neuroinflammation, neuronal apoptosis, and neurodegeneration. Additionally, the TWEAK-Fn14 axis is implicated in numerous pathophysiological events in the heart, such as cardiomyocyte proliferation, inflammation, apoptosis, hypertrophy, fibrosis, contractile function disruption, and ventricular dilatation. Given its significant contributions to CCVDs, the TWEAK-Fn14 axis has also emerged as a promising therapeutic target for BHS. In this review, the critical roles of TWEAK-Fn14 in CCVDs and its potential interplay between the brain-heart axis in BHS were updated and discussed, which shed a new light on co-treatment of brain and heart and brain-heart syndrome.

Keywords: TWEAK-Fn14, Cardiovascular Diseases, cerebrovascular diseases, Brain-heart syndrome, Immuno-inflammation

Received: 21 Sep 2025; Accepted: 01 Dec 2025.

Copyright: © 2025 Fei, Jun, Jiang, Guan, Liang, Cheng, Xiao, Guo, Fan, Zhu and Lyu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ming Lyu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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