Improving effect of physical exercise on heart failure: Reducing oxidative stress-induced inflammation by restoring Ca2+ homeostasis

• Published in: Molecular and cellular biochemistry
• Main Authors: Yuan, Shunling, Kuai, Zhongkai, Zhao, Fei, Xu, Diqun, Wu, Weijia
• Format: Journal Article
• Language: English
• Published: 04.10.2024
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-024-05124-8

Heart failure (HF) is associated with the occurrence of mitochondrial dysfunction. ATP produced by mitochondria through the tricarboxylic acid cycle is the main source of energy for the heart. Excessive release of Ca2+ from myocardial sarcoplasmic reticulum (SR) in HF leads to excessive Ca2+ entering mitochondria, which leads to mitochondrial dysfunction and REDOX imbalance. Excessive accumulation of ROS leads to mitochondrial structure damage, which cannot produce and provide energy. In addition, the accumulation of a large number of ROS can activate NF-κB, leading to myocardial inflammation. Energy deficit in the myocardium has long been considered to be the main mechanism connecting mitochondrial dysfunction and systolic failure. However, exercise can improve the Ca2+ imbalance in HF and restore the Ca2+ disorder in mitochondria. Similarly, exercise activates mitochondrial dynamics to improve mitochondrial function and reshape intact mitochondrial structure, rebalance mitochondrial REDOX, reduce excessive release of ROS, and rescue cardiomyocyte energy failure in HF. In this review, we summarize recent evidence that exercise can improve Ca2+ homeostasis in the SR and activate mitochondrial dynamics, improve mitochondrial function, and reduce oxidative stress levels in HF patients, thereby reducing chronic inflammation in HF patients. The improvement of mitochondrial dynamics is beneficial for ameliorating metabolic flow bottlenecks, REDOX imbalance, ROS balance, impaired mitochondrial Ca2+ homeostasis, and inflammation. Interpretation of these findings will lead to new approaches to disease mechanisms and treatment.Heart failure (HF) is associated with the occurrence of mitochondrial dysfunction. ATP produced by mitochondria through the tricarboxylic acid cycle is the main source of energy for the heart. Excessive release of Ca2+ from myocardial sarcoplasmic reticulum (SR) in HF leads to excessive Ca2+ entering mitochondria, which leads to mitochondrial dysfunction and REDOX imbalance. Excessive accumulation of ROS leads to mitochondrial structure damage, which cannot produce and provide energy. In addition, the accumulation of a large number of ROS can activate NF-κB, leading to myocardial inflammation. Energy deficit in the myocardium has long been considered to be the main mechanism connecting mitochondrial dysfunction and systolic failure. However, exercise can improve the Ca2+ imbalance in HF and restore the Ca2+ disorder in mitochondria. Similarly, exercise activates mitochondrial dynamics to improve mitochondrial function and reshape intact mitochondrial structure, rebalance mitochondrial REDOX, reduce excessive release of ROS, and rescue cardiomyocyte energy failure in HF. In this review, we summarize recent evidence that exercise can improve Ca2+ homeostasis in the SR and activate mitochondrial dynamics, improve mitochondrial function, and reduce oxidative stress levels in HF patients, thereby reducing chronic inflammation in HF patients. The improvement of mitochondrial dynamics is beneficial for ameliorating metabolic flow bottlenecks, REDOX imbalance, ROS balance, impaired mitochondrial Ca2+ homeostasis, and inflammation. Interpretation of these findings will lead to new approaches to disease mechanisms and treatment.