Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction: A Narrative Review
Abstract
1. Introduction
2. Methodology
2.1. Literature Search Strategy
2.2. Key References Table
3. Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction
3.1. Myocardial Infarction Is Characterized by a Significant Circadian Rhythm
3.2. Effect of Circadian Rhythm Disturbances on Myocardial Infarction
3.3. KLF15 Gene: A Central Regulator of Cardiac Circadian Rhythm
3.4. The Role of KLF15 in the Pathologic Process of Myocardial Infarction
3.4.1. Modulation of the Inflammatory Response
3.4.2. Inhibition of Apoptosis
3.4.3. Regulation of Energy Metabolism
Glucose Metabolism and Cardiac Energy Supply
Homeostatic Maintenance of Lipid Metabolism
Circadian Rhythmicity of Branched-Chain Amino Acid Metabolism
4. Discussion
5. Limitations and Future Research Directions
- (1)
- Restoring KLF15 Oscillation: Reprogramming downstream gene networks by reinstating KLF15’s circadian rhythm to facilitate myocardial repair.
- (2)
- Harnessing KLF15’s Multifunctional Effects: Leveraging its anti-inflammatory, antioxidant, and metabolic regulatory properties to mitigate inflammation, reduce cardiomyocyte death, limit infarct expansion, and prevent further cardiac dysfunction.
- (3)
- Timed Intervention Strategies: Prolonging KLF15 expression during its peak or trough phases to induce compensatory upregulation and prevent infarction.
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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[3] | 2007 | Thygesen, K.; Alpert, J. S.; White, H. D.; Jaffe, A. S.; Apple, F. S.; Galvani, M.; Katus, H. A.; Newby, L. K.; Ravkilde, J.; Chaitman, B.; et al. | International diagnostic criteria for myocardial infarction. |
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[34] | 2020 | Li, L.; Li, H.; Tien, C. L.; Jain, M. K.; Zhang, L. | KLF15 maintains normal ventricular rhythm by regulating the circadian oscillation of cardiac ion channels and QT interval. |
[35] | 2012 | Jeyaraj, D.; Scheer, F. A.; Ripperger, J. A.; Haldar, S. M.; Lu, Y.; Prosdocimo, D. A.; Eapen, S. J.; Eapen, B. L.; Cui, Y.; Mahabeleshwar, G. H.; et al. | KLF15 serves as a pivotal link between circadian rhythms and cardiac function. |
[36] | 2021 | He, S.; Lu, Y.; Guo, Y.; Li, S.; Lu, X.; Shao, S.; Zhou, H.; Wang, R.; Wang, J.; Gao, P.; et al. | KLF15 exerts anti-inflammatory effects via NF-κB/MAPK inhibition. |
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Key Point | Reference(s) | Observed Effect on MI | |
---|---|---|---|
KLF15-Inflammations | NF-κB | He, S et al. (2021) [36] | KLF15 is able to attenuate inflammatory responses by inhibiting NF-κB pathway activation |
Huang, B et al. (2010) [58] | |||
MAPK | Wang, B et al. (2021) [37] | KLF15 is able to attenuate inflammatory responses by inhibiting MAPK pathway activation | |
Twist2 | Zhou, L et al. (2019) [38] | KLF15 ameliorates postmyocardial infarction injury by regulating Twist2 | |
CTRP12 | Liao, B et al. (2022) [39] | KLF15 can alleviate post-ischemic reperfusion injury by regulating CTRP1250 | |
KLF15-Apoptosis | PI3K-AKT | Zheng, H et al. (2024) [40] | KLF15 ameliorates apoptosis through the PI3K-AKT pathway |
KLF15-EnergyMetabolism | Glucose Metabolism | Nagare, T et al. (2011) [42] | KLF15 promotes the entry of glucose into cardiomyocytes for cardiac energy supply by regulating insulin secretion |
Lipid Metabolism | Fan, L et al. (2022) [72] | KLF15 maintains lipid homeostasis in the heart by regulating PPAR-δ and PPAR-γ | |
Gire, D et al. (2021) [73] | |||
Hu, Y et al. (2022) [45] | |||
Branched-Chain AminoAcid Metabolism | Sun, H et al. (2016) [46] | KLF15 improves cardiac function by regulating BCKAs | |
Jeyaraj, D et al. (2012) [35] |
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Zhao, J.; Chen, Z.; Yang, J.; Duan, L.; Yang, H.; Cai, D.; Zhao, Z. Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction: A Narrative Review. Int. J. Mol. Sci. 2025, 26, 4831. https://doi.org/10.3390/ijms26104831
Zhao J, Chen Z, Yang J, Duan L, Yang H, Cai D, Zhao Z. Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction: A Narrative Review. International Journal of Molecular Sciences. 2025; 26(10):4831. https://doi.org/10.3390/ijms26104831
Chicago/Turabian StyleZhao, Junxin, Zhuoyang Chen, Jingyi Yang, Lincheng Duan, Hong Yang, Dingjun Cai, and Zhengyu Zhao. 2025. "Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction: A Narrative Review" International Journal of Molecular Sciences 26, no. 10: 4831. https://doi.org/10.3390/ijms26104831
APA StyleZhao, J., Chen, Z., Yang, J., Duan, L., Yang, H., Cai, D., & Zhao, Z. (2025). Effect of KLF15-Mediated Circadian Rhythm on Myocardial Infarction: A Narrative Review. International Journal of Molecular Sciences, 26(10), 4831. https://doi.org/10.3390/ijms26104831