Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise

J Cardiovasc Transl Res. 2025 Apr;18(2):442-456. doi: 10.1007/s12265-025-10591-5. Epub 2025 Jan 25.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Energy Metabolism*
  • Exercise Therapy*
  • Exercise*
  • Heart Failure* / metabolism
  • Heart Failure* / pathology
  • Heart Failure* / physiopathology
  • Heart Failure* / therapy
  • Humans
  • Mitochondria, Heart* / metabolism
  • Mitochondria, Heart* / pathology
  • Recovery of Function
  • Stroke Volume*
  • Treatment Outcome
  • Ventricular Function, Left*