Cardiovasc.Res：miRNA-23a可能是血管内皮细胞凋亡“元凶”

Wei Ruan, Jun-mei Xu, Suo-bei Li, Ling-qing Yuan and Ru-ping Dai

Aims: Endothelial cell injury induced by inflammatory factors plays a critical role in the pathogenesis of numerous vascular diseases.microRNAs are well known to be implicated in the cell proliferation and apoptosis in the inflammatory responses. However, it remains to be determined whether microRNAs are associated with tumor necrosis factor (TNF)-α-mediated endothelial cell injury. The aim of the present study is to investigate the role of microRNAs in TNF-α-induced endothelial cell apoptosis. Methods and results: Microarrays were used to analyze the global expression of microRNAs in TNF-α-stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT-PCR. After TNF-α treatment, twelve miRNAs were dramatically up-regulated and nine were down-regulated. LNA-anti-miR-23a and pre-miR-23a were found to modulate one of the markedly down-regulated miRNAs, miR-23a, which could in turn increase or attenuate TNF-α-induced endothelial cell apoptosis. Bioinformatics analysis suggested that caspase-7 and serine/threonine kinase 4 (STK4) are potential targets of miR-23a. LNA-anti-miR-23a enhanced, but pre-miR-23a inhibited the activation of caspase-7, STK4 and its related signaling caspase-3 after TNF-α treatment. However, pre-miR-23a or LNA-anti-miR-23a had no effect on TNF-α-induced Bcl-2 activation. Conclusion: Our results suggest that miR-23a may be involved in TNF-α-induced endothelial cell apoptosis through regulation of the caspase-7 and STK-4-caspase-3 pathways.