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Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review)

  • Authors:
    • Junwei Gao
    • Lingyao Li
    • Siqi Zhai
    • Yan Dong
    • Zhiyi Zhang
    • Duomao Lin
    • Jun Ma
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of Anesthesiology, The First Hospital of Tsinghua University, Beijing 100016, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 191
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    Published online on: September 10, 2025
       https://doi.org/10.3892/ijmm.2025.5632
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Abstract

Myocardial ischemia reperfusion injury (MIRI) remains a key and difficult issue in the field of cardiovascular diseases, and its pathogenesis involves multiple aspects. Exercise can effectively improve MIRI, and the mechanisms include reducing oxidative stress and inflammatory responses, regulating mitochondrial function and metabolic abnormalities, and so on. For patients undergoing reperfusion, rehabilitation therapy mainly based on exercise has important clinical significance. The present study expounded on the occurrence of MIRI from the perspective of mechanisms and the improvement effect of exercise on MIRI, elaborates on the main current exercise strategies and existing problems from the aspect of clinical practice, and discusses the possible future development directions.
View Figures

Figure 1

Pathological mechanisms of MIRI. (A)
Oxidative Stress; (B) Calcium Overload; (C) Energy Metabolism
Disorder; (D) Inflammation; (E) Mitochondrial Dysfunction; (F) MQC
Disorder. MIRI, myocardial ischemia reperfusion injury; MQC,
mitochondrial quality control; OMM, outer mitochondrial membrane;
IMM, inner mitochondrial membrane; IMS, intermembrane space; NADH,
nicotinamide adenine dinucleotide, FADH2, flavine
adenine dinucleotide, reduced; UQ, ubiquinone; Cyt c, cytochrome
c; mPTP, mitochondrial permeability transition pore; ROS,
reactive oxygen species; ADP, adenosine diphosphate; ATP, adenosine
triphosphate; Na+, sodium ion; Ca2+, calcium
ion; H+, hydrogen ion; NHE, sodium-hydrogen exchanger;
NCX, sodium-calcium exchanger; TCA, tricarboxylic acid cycle;
DAMPs, damage-associated molecular patterns; IL-1α, interleukin-1
α; mtDNA, mitochondrial DNA; TLR, Toll-like receptor; NF-κB,
nuclear factor κ B.

Figure 2

The key mechanisms by which exercise
ameliorates MIRI. (A) Exercise induced the eNOS/NO and protein S-NO
pathway in the mitochondria, leading to reduced mitochondrial ROS
production and mPTP activation and thus conveying cardioprotection
against I/R injury. (B) AKT-mediated HKII-mitochondrial interaction
due to exercise protects mitochondria by inhibiting mitochondrial
apoptotic cascades and contributes to the increased
cardioprotection against MIRI. (C) Exercise-induced CPhar elevation
could prevent MIRI and cardiac dysfunction. Mechanically, CPhar can
act as binding partner of DDX17 to inhibit the expression of
downstream molecule ATF7 through sequestering C/EBPβ. (D) Voluntary
exercise reduced leptin production in adipose tissue, enhanced the
quiescence-promoting hematopoietic niche factors in leptin
receptor-positive stromal bone marrow cells and decreased
hematopoietic activity, reducing the generation of inflammatory
white blood cells and providing protection against myocardial
damage. MIRI, myocardial ischemia reperfusion injury; eNOS,
endothelial nitric oxidase synthases; NO, nitric oxide; S-NO,
S-nitrosylation; ROS, reactive oxygen species; mPTP, mitochondrial
permeability transition pore; I/R, ischemia/reperfusion; AKT,
protein kinase B; HKII, Hexokinase II; CPhar, Cardiac Physiological
Hypertrophy-Associated Regulator; ATF7, activating transcription
factor 7; Ca2+, calcium ion; TCA, tricarboxylic acid
cycle; VDAC, voltage dependent anion channel; DRP, dynamin-related
protein; BAX, BCL2-Associated X; P, phosphorylation; DDX17,
DEAD-Box Helicase 17; C/EBPβ, CCAAT/enhancer binding protein beta;
CXCL12, C-X-C Motif Chemokine Ligand 12; CVD, cardiovascular
disease.

Figure 3

Figure 4

Digital technologies in home-based
CR. CR, cardiac rehabilitation; HIIT, high-intensity interval
training; HR, heart rate; AI, artificial intelligence.
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Copy and paste a formatted citation
Spandidos Publications style
Gao J, Li L, Zhai S, Dong Y, Zhang Z, Lin D and Ma J: Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review). Int J Mol Med 56: 191, 2025.
APA
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., & Ma, J. (2025). Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review). International Journal of Molecular Medicine, 56, 191. https://doi.org/10.3892/ijmm.2025.5632
MLA
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., Ma, J."Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review)". International Journal of Molecular Medicine 56.5 (2025): 191.
Chicago
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., Ma, J."Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 191. https://doi.org/10.3892/ijmm.2025.5632
Copy and paste a formatted citation
x
Spandidos Publications style
Gao J, Li L, Zhai S, Dong Y, Zhang Z, Lin D and Ma J: Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review). Int J Mol Med 56: 191, 2025.
APA
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., & Ma, J. (2025). Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review). International Journal of Molecular Medicine, 56, 191. https://doi.org/10.3892/ijmm.2025.5632
MLA
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., Ma, J."Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review)". International Journal of Molecular Medicine 56.5 (2025): 191.
Chicago
Gao, J., Li, L., Zhai, S., Dong, Y., Zhang, Z., Lin, D., Ma, J."Exercise training for myocardial ischemia reperfusion injury: Mechanism and clinical practice (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 191. https://doi.org/10.3892/ijmm.2025.5632
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