Molecular Mechanisms and Signaling Pathways of Myocardial Ischemia: A Multidimensional Analysis from Energy Metabolism to Cell Death

YIWEI HAO^1,#, YAODONG PING^2,#, YAN YANG³, CHENG QU³, YUAN CHEN¹, XUEYAN JIANG¹, RONG FU¹, HAILONG ZHAO^4,*, LEI YU^4,*
1 Peking University Cancer Hospital (Inner Mongolia Campus), Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot, 010020, China,
2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pharmacy, Peking University Cancer Hospital Institute, Beijing, 100142, China
3 School of Pharmacy, Inner Mongolia Medical University, Hohhot, 010110, China
4 Department of Pharmacy, Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, 010010, China
* Corresponding Author: HAILONG ZHAO. Email: email ; LEI YU. Email: email
# These authors contributed equally to this work

BIOCELL https://doi.org/10.32604/biocell.2025.074863

Received 20 October 2025; Accepted 13 December 2025; Published online 29 December 2025

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Abstract

Myocardial ischemia, a core pathological process underlying diverse cardiovascular diseases such as coronary artery disease, poses a severe threat to global human health by frequently leading to acute myocardial infarction, heart failure, and even sudden cardiac death. A comprehensive understanding of its intricate underlying pathogenic mechanisms is not only crucial for developing effective therapeutic strategies but also essential for accelerating the translation of basic research findings into clinical practice. However, the complex regulatory networks that drive myocardial ischemia remain to be systematically clarified. These networks encompass the intricate interactions among multiple pathological processes, including energy metabolism disorder, intracellular calcium overload, mitochondrial structural and functional dysfunction, excessive oxidative stress, persistent inflammatory response, cardiomyocyte apoptosis, and autophagic imbalance. While existing research has laid a preliminary foundation by exploring individual mechanisms, it lacks an integrated overview of how these pathological processes synergistically or sequentially intertwine to induce progressive myocardial cell injury and irreversible cardiac dysfunction. Therefore, this review aims to systematically summarize the latest research advancements on the key molecular mechanisms and critical signaling pathways involved in myocardial ischemia. It will specifically focus on dissecting the dynamic crosstalk between different pathological processes, with the ultimate objective of providing a solid theoretical basis for the development of multi-targeted precision therapy. This work is expected to offer new insights into the pathological progression of myocardial ischemia and further guide the design and development of innovative clinical intervention strategies.