Platelet-derived exosomes regulate endothelial cell inflammation and M1 macrophage polarization in coronary artery thrombosis via modulating miR-34a-5p expression

作者：Kangkang Wei, Lintong Yu, Jinming Li, Jie Gao, Li Chen, Min Liu, Xiaohan Zhao, Min Li, Dazhuo Shi, Xiaojuan Ma · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-67654-x · 被引用次数：16 · 研究领域：Extracellular vesicles in disease、Cardiovascular Disease and Adiposity、MicroRNA in disease regulation

As the important factors in coronary artery thrombosis, endothelial injury and M1 macrophage polarization are closely related to the expression of miR-34a-5p. Exosomes in plasma are mainly derived from platelets and play an important role in thrombosis. Based on these facts, this study was conducted to investigate the acting mechanism of platelet-derived exosomes (PLT-exo) in the effects of endothelial injury and M1 macrophage polarization on coronary artery thrombosis. Firstly, rats were divided into the sham-operated group and the coronary microembolization (CME) group, and their plasma-derived exosomes were extracted to detect the expression of miR-34a-5p. Next, the PLT-exo were extracted from healthy volunteers and then co-cultured with ox-LDL-induced endothelial cells and LPS-induced macrophages, respectively. Subsequently, the expression of IL-1β, IL-6, TNF-α, and ICAM-1 in endothelial cells was measured, and the level of markers related to M1 macrophage polarization and Sirt1/NF-κB pathway was detected. Finally, the above indicators were examined again after PLT-exo combined with miR-34a-5p mimic were co-cultured with endothelial cells and macrophages, respectively. The results demonstrated that the expression of miR-34a-5p in the CME group was up-regulated compared with the sham-operated group. In cell experiments, PLT-exo modulated the Sirt1/NF-κB pathway by inhibiting the expression of intracellular miR-34a-5p and down-regulated the expression of IL-1β, IL-6, TNF-α,...