Low shear stress induced vascular endothelial cell pyroptosis by TET2/SDHB/ROS pathway.

Vascular endothelial cell (VEC) inflammation induced by low shear stress plays key roles in the initiation and progression of atherosclerosis (As). Pyroptosis is a form of inflammatory programmed cell death that is critical for As. However, the effect of low shear stress on VEC pyroptosis and the underlying mechanisms were not clear. Here we show that low shear stress promoted VEC pyroptosis and reduced the expression of Ten-Eleven Translocation 2 (TET2) methylcytosine dioxygenase. Loss of TET2 resulted in the upregulation of the expression and activity of mitochondrial respiratory complex II subunit succinate dehydrogenase B (SDHB) by decreasing the recruitment of histone deacetylase 2, independent of DNA demethylation modification. The overexpression of SDHB mediated mitochondrial injury and increased the production of reactive oxygen species (ROS). The administration of ROS scavenger NAC alleviated VEC pyroptosis induced by SDHB overexpression and TET2 shRNA. These findings show that low shear stress induced endothelial cell pyroptosis through the TET2/SDHB/ROS pathway and offer new insights into As. Image 1 • Low shear stress promotes vascular endothelial cell pyroptosis through the TET2/SDHB/ROS pathway. • The higher expression of succinate dehydrogenase B contributes to mitochondrial injury and ROS production. • TET2 regulates the expression of SDHB by recruiting HDAC2, independent on DNA methylation and hydroxymethylation. [ABSTRACT FROM AUTHOR]