Salvianolic Acid B Upregulates miR-744-5p Expression in Peripheral Blood Mononuclear Cell–Derived Extracellular Vesicles to Alleviate Uremic Cardiomyopathy

Abstract

Uremic cardiomyopathy (UCM) is a severe complication of uraemia that lacks effective treatments. The role of immune dysfunction in haemodialysis patients with UCM remains unclear. Peripheral blood mononuclear cells (PBMCs) are major components of the immune system; however, they do not directly contact cardiomyocytes. In general, extracellular vesicles (EVs) function as intercellular communication mediators. Therefore, in this study, we first investigated the role of PBMC-derived EVs (PBMC-EVs) in UCM and identified EV-miR-744-5p as a key molecule involved in PBMC–cardiomyocyte communication. Mechanistically, indoxyl sulphate (IS) downregulated miR-744-5p expression in PBMC-EVs, leading to IGF2R upregulation in cardiomyocytes, thereby exacerbating myocardial injury via induction of hypertrophy, apoptosis and inflammatory pathway activation in the cardiomyocytes. We also explored the potential of natural products to treat UCM by modifying PBMC-EVs and found that the traditional Chinese medicine monomer salvianolic acid B (Sal B) could bind to YY1, enhancing miR-744-5p expression in PBMC-EVs and thus mitigating myocardial injury in UCM. Taken together, these findings indicate the critical role of PBMC-EVs in UCM and suggest the cardioprotective effects of Sal B via PBMC-EV modification. They also provide novel insights into immune mechanisms underlying UCM, particularly indicating that targeting PBMC-EVs may be a promising UCM treatment strategy.