Review

. 2025 Apr;18(2):442-456.

doi: 10.1007/s12265-025-10591-5. Epub 2025 Jan 25.

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise

Xinxin Cui^#^{1

2}, Michail Spanos^#^{3

4}, Cuimei Zhao^#⁵, Wensi Wan², Caiyue Cui², Lijun Wang^{6

7}, Junjie Xiao^{8

9}

Affiliations

¹ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
² Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China.
³ Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
⁴ Albert Einstein College of Medicine, Department of Internal Medicine, NCB, Bronx, NY, USA.
⁵ Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
⁶ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China. lijunwang@shu.edu.cn.
⁷ Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China. lijunwang@shu.edu.cn.
⁸ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China. junjiexiao@shu.edu.cn.
⁹ Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China. junjiexiao@shu.edu.cn.

^# Contributed equally.

PMID: 39863753
DOI: 10.1007/s12265-025-10591-5

Review

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise

Xinxin Cui et al. J Cardiovasc Transl Res. 2025 Apr.

. 2025 Apr;18(2):442-456.

doi: 10.1007/s12265-025-10591-5. Epub 2025 Jan 25.

Authors

Xinxin Cui^#^{1

2}, Michail Spanos^#^{3

4}, Cuimei Zhao^#⁵, Wensi Wan², Caiyue Cui², Lijun Wang^{6

7}, Junjie Xiao^{8

9}

Affiliations

¹ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
² Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China.
³ Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
⁴ Albert Einstein College of Medicine, Department of Internal Medicine, NCB, Bronx, NY, USA.
⁵ Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
⁶ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China. lijunwang@shu.edu.cn.
⁷ Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China. lijunwang@shu.edu.cn.
⁸ Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China. junjiexiao@shu.edu.cn.
⁹ Institute of Cardiovascular Sciences, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai Engineering Research Center of Organ Repair, Shanghai University, Shanghai, China. junjiexiao@shu.edu.cn.

^# Contributed equally.

PMID: 39863753
DOI: 10.1007/s12265-025-10591-5

Abstract

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca²⁺ regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis. Exercise plays a vital role in preserving mitochondrial homeostasis, thereby protecting the cardiovascular system from acute stress, and is a fundamental component in maintaining cardiovascular health. In this study, we review the mitochondrial dysfunction underlying the development and progression of HFpEF. Given the pivotal role of exercise in modulating cardiovascular diseases, we particularly focus on exercise as a potential therapeutic strategy for improving mitochondrial function. Graphical abstract Note: This picture was created with BioRender.com.

Keywords: Exercise; Heart failure with preserved ejection fraction; Mitochondria; Mitochondrial dynamics; Oxidative stress.

PubMed Disclaimer

Conflict of interest statement

Declarations. Disclosures: Dr. Junjie XIAO is an associate editor of Journal of Cardiovascular Translational Research. Dr. Lijun Wang is an editorial board member of Journal of Cardiovascular Translational Research. The other authors declare no competing interests. Ethics Approval and Consent to Participate: Not applicable. Informed Consent: Not applicable.

Cited by

Advances in pathophysiological mechanisms and therapeutic efficacy of exercise rehabilitation in patients with heart failure with preserved ejection fraction.
Fang J, Wang Z, Yu J. Fang J, et al. Front Cardiovasc Med. 2025 May 27;12:1598878. doi: 10.3389/fcvm.2025.1598878. eCollection 2025. Front Cardiovasc Med. 2025. PMID: 40495991 Free PMC article. Review.
Mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF).
Pecchia B, Samuel R, Shah V, Newman E, Gibson GT. Pecchia B, et al. Heart Fail Rev. 2025 Jul;30(4):777-789. doi: 10.1007/s10741-025-10504-3. Epub 2025 Mar 13. Heart Fail Rev. 2025. PMID: 40080287 Free PMC article. Review.
Coronary microvascular disease in heart failure with preserved ejection fraction.
Sen P, Wang L, d'Ambrosio L, Bierschenk S, Hamers J, Ornek I, Sittig T, Zhang H, Zhang J, Merkus D. Sen P, et al. Physiol Rep. 2025 Aug;13(16):e70521. doi: 10.14814/phy2.70521. Physiol Rep. 2025. PMID: 40834289 Free PMC article. Review.

References

1. Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, Obokata M, Rider OJ. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res. 2023;118:3434–50. - PubMed
1. Peng C, Zhang Y, Lang X, Zhang Y. Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis. J Transl Med. 2023;21:66. - PubMed - PMC
1. Wu C, Zhang Z, Zhang W, Liu X. Mitochondrial dysfunction and mitochondrial therapies in heart failure. Pharmacol Res. 2022;175:106038. - PubMed
1. Qiu Y, Fernandez-Garcia B, Lehmann HI, Li G, Kroemer G, Lopez-Otin C, Xiao J. Exercise sustains the hallmarks of health. J Sport Health Sci. 2023;12:8–35. - PubMed
1. Xiao J, Rosenzweig A. Exercise and cardiovascular protection: Update and future. J Sport Health Sci. 2021;10:607–8. - PubMed - PMC

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Springer
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise

Affiliations

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous