Cell death and inflammation play critical roles in atherosclerosis. Pyroptosis, a novel proinflammatory programmed cell death process, participates in atherosclerosis pathogenesis. Recently, MALATI was identified as a pyroptosis-related long noncoding RNA (IncRNA). Here, we investigated the potential role and underlying mechanism of IncRNA MALATI in endothelial cells pyroptosis. We first established an endothelial cell pyroptosis model by stimulating EA.hy926 human endothelial cells (EA.hy926 cells) with high glucose. Then, we investigated IncRNA MALAT1 expression and found that it was upregulated in high glucose-treated EA.hy926 cells. Furthermore, IncRNA MALATI knockdown significantly inhibited high glucose-induced pyroptosis in EA.hy926 cells, which may critically influence atherosclerosis. Moreover, miR-22 was a target of IncRNA MALATI and was negatively correlated with IncRNA MALATI. NLRP3 expression was significantly suppressed by transfection with a MALATI-targeting antisense oligonucleotide (ASO). Ultimately, miR-22 overexpression abrogated the effect of MALATI on high glucose-induced EA.hy926 cells pyroptosis. Together, our results suggest that IncRNA MALATI promotes high glucose-induced pyroptosis of endothelial cells partly by affecting NLRP3 expression through competitively binding miR-22. Our findings indicate a new regulatory mechanism for endothelial cells pyroptosis under high-glucose stress, providing a novel therapeutic target for atherosclerosis. (C) 2018 Elsevier Inc. All rights reserved.