Magnesium alloy (Mg
alloy) has attracted massive attention in the potential applications of cardiovascular
stents because of its good biocompatibility and degradability. However, whether and how the Mg
alloy induces
inflammation in endothelial cells remains unclear. In the present work, we investigated the activation of Yes-associated
protein (YAP) upon Mg
alloy stimuli and unveiled the transcriptional function in Mg
alloy-induced
inflammation. Quantitative RT-PCR, western blotting and immunofluorescence staining showed that Mg
alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells (HCAECs).
Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg
alloy-derived
inflammation. This led to the observation that nuclear YAP further bonded to the promoter region of
inflammation transcription factors and co-
transcription factors. This binding event activated their transcription and modified
mRNA methylation of
inflammation-related genes through regulating the expression of
N6-methyladenosine modulators (METTL3, METTL14, FTO and WTAP). This then promoted
inflammation-related gene expression and aggravated
inflammation in HCAECs. In YAP deficiency cells, Mg
alloy-induced
inflammation was reduced. Collectively, our data suggest that YAP contributes to the Mg
alloy-derived
inflammation in HCAECs and may provide a potential therapeutic target that alleviates
inflammation after Mg
alloy stent implantation.