Pyroptosis is a form of cell death that is uniquely dependent on caspase-1. Pyroptosis involved in oxidized low-density lipoprotein (ox-LDL)-induced human macrophage death through promotion of caspase-1 activation is important for formation of unstable plaques in atherosclerosis. The mitochondrial outer membrane protein NIX directly interacts with microtubule-associated protein 1 light chain 3 (LC3). Although we previously showed that NIX-mediated mitochondrial autophagy is involved in the clearance of damaged mitochondria, how NIX contributes to ox-LDL-induced macrophage pyroptosis remained unknown. Here, Immunoperoxidase staining Nix expression decreased in human atherosclerosis. When we silenced NIX expression in murine macrophage cell, active caspase-1 and mature interleukin 1β(IL-1β) expression levels were increased and LC3 was reduced. In addition, LDH release and acridine orange and ethidium bromide staining indicated that damage to macrophage cell membranes induced by ox-LDL was substantially worse. Moreover, intracellular ROS and NLRP3 inflammasome levels increased. Taken together, these results demonstrated that NIX inhibits ox-LDL-induced macrophage pyroptosis via autophagy in atherosclerosis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.