The roles of exosomes in the pathogenesis and treatment of coronary heart disease with depression and/or anxiety

Coronary heart disease (CHD) patients have been found to also possess high anxiety and depression rates, which have been considered as significant risk factors for the disease. One possible underlying biological mechanism behind anxiety/depression being associated with CHD may be exosomes, extracellular vesicles produced by cells throughout the body. These exosomes contain various proteins and miRNAs that could exert a variety of physiological and pathological effects. However, the precise role they play in CHD with anxiety/depression has still not been fully elucidated. In this review, we summarized the current research on exosome involvement in the pathogenesis of CHD with anxiety/depression, particularly focusing on inflammatory responses, neuroendocrine signaling, sympathetic nervous system (SNS) regulation, platelet activation, and endothelial injury. In particular, for inflammatory responses, exosomes have been associated with increased pro-inflammatory cytokine release, such as interleukin (IL)-1β, while for neuroendocrine signaling, the miRNAs miR-135a-5p and miR-320a have been implicated in increasing glucocorticoid signaling. As for SNS regulation, exosome miRNAs are involved in downregulating Nrf2, leading to increased sympathetic nerve excitation, while inhibiting exosome production counteracts platelet activation, in turn lowering thrombosis risk for CHD. Endothelial dysfunction could be promoted by exosomes carrying miR-155. On the other hand, exosome contents exert beneficial effects that could be used for treatment strategies, such as miR-1246 alleviating hypoxia-induced myocardial tissue damage, as well as miR-188–3p lowering nigrostriatal autophagy. Overall, identifying the roles that exosomes play in CHD with concurrent anxiety/depression pathogenesis, as well as potential alleviation, may be greatly beneficial for formulating effective treatment strategies.