Role of Exercise in Modulating the Brain–Heart Axis in Cardiovascular Diseases

Figures

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  Figure 1. The brain–heart axis is composed of key autonomic neural networks and conduction systems. On the coronal plane of the brain, the autonomic neural network of the brain–heart axis is illustrated. Efferent pathways originate from the medial prefrontal cortex and insular cortex, terminating at cardiomyocytes and arterial endothelial cells. Afferent pathways begin with inputs from chemoreceptors and baroreceptors, ultimately projecting to higher cortical centers.

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  Figure 2. The imbalance of the brain–heart axis aggravates cardiovascular damage. Psychological stress and emotional disorders such as depression can trigger dysfunction of the HPA axis and the SNS. In this state, sympathetic overactivation leads to the excessive release of catecholamines (e.g., norepinephrine and epinephrine), accompanied by reduced HRV. Sustained activation of the HPA axis promotes the secretion of CRH and ACTH, thereby exacerbating systemic stress levels. This excessive catecholaminergic stimulation elevates heart rate and blood pressure, disrupting the myocardial oxygen supply-demand balance and consequently aggravating cardiac injury. Meanwhile, chronic HPA axis activation induces elevated expression of pro-inflammatory cytokines, which persistently damages the cardiovascular system. Furthermore, inflammatory mediators released by the injured heart, together with adverse cardiac symptoms, feedback on the central nervous system, perpetuating a detrimental heart–brain crosstalk loop. Abbreviations: ACTH adrenocorticotropic hormone, BRS baroreflex sensitivity, BP blood pressure, CRH corticotropin-releasing hormone, HRV heart rate variability, IL-6 interleukin-6, PNS…

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  Figure 3. The central and peripheral mechanisms by which exercise regulates the brain–heart axis. Exercise influences key components of the central autonomic network to rebalance sympathetic and parasympathetic output, thereby regulating cardiac receptor signaling and improving heart rate variability. In parallel, exercise modulates the gut–brain–heart, muscle–brain–heart, spleen–brain–heart, and BAT–brain–heart axis, collectively reducing neuroinflammation, oxidative stress, apoptosis, myocardial fibrosis, and sympathetic remodeling, and ultimately contributing to cardiovascular protection. Abbreviations: Ach acetylcholine, α7nAChR, alpha 7 nicotinic acetylcholine receptor; β1-AR, β1-adrenergic receptor; β2-AR, β2-adrenergic receptor, BAT brown adipose tissue, BDNF brain-derived neurotrophic factor, CTSB cathepsin B, EVs extracellular vesicles, HRV heart rate variability, IGF-1 insulin-like growth factor-1, IL-6 interleukin-6, LC locus coeruleus, LepR leptin receptor, M1 primary motor cortex, mPFC medial prefrontal cortex, M2-R M2 muscarinic receptor, miR-21 microRNA-21, miR-29c-3p microRNA-29c-3p, miR-30c microRNA-30c, NST nucleus of the solitary tract, PAG periaqueductal gray, PVN…

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  Figure 4. Potential central mechanisms by which exercise improves cardiovascular function via the brain–heart axis. Exercise improves cardiovascular function through several central pathways: by suppressing central inflammatory responses and regulating immune function, promoting neuronal plasticity, ameliorating neuroendocrine dysregulation and promoting the secretion of exerkines. ACTH adrenocorticotropic hormone, ANG I angiotensin I, ANG II angiotensin II, AT1 angiotensin II type 1 receptor, BDNF brain-derived neurotrophic factor, CRH corticotropin-releasing hormone, CTSB cathepsin B, FGF21 fibroblast growth factor 21, GPLD1 glycosylphosphatidylinositol specific phospholipase D1.