TNF and atherosclerosis: When atherosclerosis occurs, various types of cells, especially SMCs, endothelial cells and macrophages in the injured vessels produce large amounts of PCSK9 at the transcriptional and translational levels in response to the stimulation of low shear stress, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), ox-LDL, reactive oxygen species (ROS), and mitochondrial DNA (mtDNA) and mitochondria-derived reactive oxygen species (mtROS) released from damaged mitochondria in ruptured cells (37, 39–42).