REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
This article is part of the Research TopicExploring the impact of Inflammatory processes on the course of Acute Myocardial Infarction: Pathways and TherapiesView all 4 articles
Targeting the Notch Signaling Pathway: Molecular Mechanisms and Therapeutic Strategies for Cardiac Repair after Myocardial Infarction
Provisionally accepted
- 1The People's hospital of Yuhuan, Taizhou, China
- 2Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China
- 3Tongji Hospital Affiliated to Tongji University, Shanghai, China
- 4Nanjing University of Chinese Medicine, Nanjing, China
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Myocardial infarction (MI) is a leading cause of death globally and is characterized by extensive cardiomyocyte death, fibrosis, and diminished cardiac function, leading to heart failure. The limited regenerative capacity and excessive fibrosis of the heart highlight the need for effective therapeutic strategies. The Notch signaling pathway, known for its role in cell fate determination and tissue repair, is transiently activated after MI in cardiomyocytes, endothelial cells, and smooth muscle cells. This activation modulates cardiac repair by reducing oxidative stress and apoptosis, regulating inflammation, promoting angiogenesis, and inhibiting fibrosis. Recent research has focused on targeting the Notch pathway to increase myocardial regeneration and angiogenesis via the use of gene therapy, small-molecule regulators, and cell-based therapies. For example, delivering Notch ligands through hydrogels has yielded promising results in preclinical studies, enhancing cardiac function and promoting angiogenesis. This review examines the molecular mechanisms by which Notch signaling influences cardiac repair post-MI. We also discuss its specific roles in cardiomyocyte regeneration, fibrosis inhibition, and angiogenesis enhancement. Additionally, this study evaluated the therapeutic potential of Notch pathway modulation, addressing clinical translation challenges, safety concerns, and the importance of personalized treatment strategies. Future research directions include leveraging gene editing and nanotechnology-based drug delivery to improve the efficacy and safety of Notch-targeted therapies for cardiovascular diseases.
Keywords: Notch signaling pathway, Myocardial Infarction, Cardiac repair, Cardiomyocyte regeneration, Angiogenesis
Received: 19 Jul 2025; Accepted: 06 Nov 2025.
Copyright: © 2025 Zhang, Xie, Cheng, Liu, Wang, Long, Feng and Yuan. 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:
Jun Long, longjun@njucm.edu.cn
QiMao Feng, fenqimao@126.com
DongPing Yuan, dpyuan@njucm.edu.cn
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.