Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction

Abstract

Inflammation mediated by myeloid cells trigger receptors 1 (TREM-1) is important for atherosclerosis development, while sirtuin 6 (Sirt6) levels decrease in atheroscleoritc plaque. Here we demonstrate that oxidatively modified low density lipoprotein (ox-LDL)-treated endothelial cells (ECs) exhibited increased TREM-1-mediated pyroptosis and decreased Sirt6-induced autophagy. We show that high sTREM-1 and low sSirt6 levels were independent predictors of boosted endothelial microparticles (EMPs) on admission, and were associated with increased risk for all-cause mortality and major adverse cardiovascular events (MACE) at median 24 months (interquartile range, 18–26) follow-up in acute myocardial infarction (AMI) patients. Additionally, blockage of Sirt6-induced autophagy led to augmented TREM-1-mediated pyroptosis, whereas Sirt6 overexpression attenuated ECs inflammation and pyroptosis following ox-LDL treatment. Our findings indicate that TREM-1 and in a reversed trend Sirt6 appeared to be markers of endothelial inflammation with potential for use in risk stratification.