Exercise is a highly cost-effective and non-pharmacological intervention for maintaining cardiovascular health and treating heart diseases. Exercise can protect the heart through multiple effects, including regulations of cardiomyocytes and non-cardiomyocytes. Immune cells can be regulated upon exercise under both physiological and pathological conditions. The present review presents the current knowledge and research advances about how exercise protects the heart, especially deciphering the regulation of cardiomyocytes and immune microenvironment by exercise. This review introduces the effect of exercise on the infiltration, phenotypic plasticity, and activation of innate and adaptive immune cells, alongside their interactions with other cellular components within the cardiac immune microenvironment. Moreover, we address the role of lymphatic vessels in regulating immune cell trafficking and activation, as well as the effects of exercise on cardiac lymphangiogenesis. It further discusses the application of multi-omics approaches in investigating exercise-induced cardiac adaptations, explores potential therapeutic strategies targeting the cardiac immune microenvironment, and highlights the cardiotoxicity risks associated with excessive exercise. A deep understanding of the effects of exercise on cardiomyocytes and cardiac immune microenvironment will pave the way to promote the exercise interventions and the development of exercise-mimetics in the treatment of heart diseases.
Keywords: Cardiac Health; Cardiomyocytes; Exercise; Immune Cells; Immune Microenvironment; Lymphangiogenesis.