Tissue-Specific Angiogenic Responses to Exercise: Mechanisms and Research Advances

Exercise is a pivotal non-pharmacological intervention for enhancing overall health, with a key underlying mechanism being the induction of adaptive angiogenesis across multiple organ systems. This narrative review discusses recent advances in exercise-induced angiogenesis, with a particular focus on its tissue- and organ-specific manifestations and underlying molecular mechanisms. The available evidence indicates that exercise integrates diverse signals-including mechanical stress, metabolic shifts, and hypoxic or ischemic stress-to upregulate key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), and to activate conserved signaling pathways including hypoxia-inducible factor-1α (HIF-1α), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and endothelial nitric oxide synthase (eNOS), thereby driving angiogenesis. This process exhibits tissue specificity: in skeletal muscle, it primarily enhances oxygen transport and metabolic efficiency; in bone, it couples with osteogenesis to maintain structural integrity; in the brain, it supports neuroplasticity and cognitive function; in the heart, it improves myocardial perfusion via angiogenesis and collateral remodeling (arteriogenesis); and in adipose tissue, it ameliorates the metabolic microenvironment. Furthermore, the mode and intensity of exercise, along with individual differences (such as age and health status), significantly influence the magnitude of its angiogenic effects. Accordingly, this review highlights the proposed role of exercise-induced angiogenesis in a range of conditions-including cardiovascular disease, sarcopenia, osteoporosis, neurodegenerative disorders, and metabolic syndrome-and we treat these relationships as potential mechanisms that require further validation rather than established therapeutic pathways. In the future, research should aim to define optimal exercise parameters, elucidate deeper molecular mechanisms, and investigate the translational potential of these insights for personalized clinical interventions.