MiR-27b attenuates mitochondrial oxidative stress and inflammation in endothelial cells

MiR-27b is highly expressed in endothelial cells (EC) but its function in this context is poorly characterized. This study aims to investigate the effect of miR-27b on inflammatory pathways, cell cycle, apoptosis, and mito-chondrial oxidative imbalances in immortalized human aortic endothelial cells (teloHAEC), human umbilical vein endothelial cells (HUVEC), and human coronary artery endothelial cells (HCAEC) exposed to TNF-alpha. Treatment with TNF-alpha downregulates the expression of miR-27b in all EC lines, promotes the activation of in-flammatory pathways, induces mitochondrial alteration and reactive oxygen species accumulation, fostering the induction of intrinsic apoptosis. Moreover, miR-27b mimic counteracts the TNF-alpha-related cytotoxicity and inflammation, as well as cell cycle arrest and caspase-3-dependent apoptosis, restoring mitochondria redox state, function, and membrane polarization. Mechanistically, hsa-miR-27b-3p targets the 3 ' untranslated regions of FOXO1 mRNA to downregulate its expression, blunting the activation of the Akt/FOXO1 pathway. Here, we show that miR-27b is involved in the regulation of a broad range of functionally intertwined phenomena in EC, suggesting its key role in mitigating mithochondrial oxidative stress and inflammation, most likely through targeting of FOXO1. Overall, results reveal for the first time that miR-27b could represent a possible target for future therapies aimed at improving endothelial health.

Automated summary

miR-27b is highly expressed in endothelial cells and plays a crucial role in regulating inflammatory pathways, cell cycle, apoptosis, and mitochondrial oxidative imbalances. miR-27b mimic can counteract the cytotoxicity and inflammation caused by TNF-alpha, as well as restore mitochondrial function. Mechanistically, miR-27b targets FOXO1 to achieve its functions.