Reprogramming heart failure: physiological orchestration and mechanistic decoding of exercise benefits

Heart failure (HF) is a complex clinical syndrome caused by a variety of reasons leading to structural or functional damage to the heart and a decline in the heart's pumping ability, and it is the endpoint of various cardiovascular diseases, which is based on the decompensation for myocardial cell function. In the pathophysiology of HF, pathological structures, abnormal neurohumoral, cellular reprogramming, and molecular mechanisms are activated and form a network to sustain physiological phenomena. These coordinated biochemical processes promote increased sympathetic activity and circulatory redistribution and are also accompanied by the onset of distinct, parallel clinical symptoms. Invasive and/or medicamentous procedures for HF endeavour to maintain and limit these compensatory mechanisms to the physiological range, and more strides are still needed to ameliorate patients' quality of life. Non-invasive therapeutic options (physical exercise) offer new entry points for the management of HF. Continuously optimized exercise protocols and therapeutic targets are indispensable for a deeper understanding of the fine processes by which exercise modulates HF. This review will focus on how different exercises modulate myocardial mitochondrial bioenergetics, angiogenesis, cardiogenic dementia, and microRNAs associated with HF in order to comprehensively consolidate a compact overview of basic mechanisms and of the novel unfolding, and to encourage further research in this field.