S100A8 and aneurysm: In the absence of other inflammatory stimulation, excessive free cholesterol within the membrane and/or endosomes can activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway via toll-like receptor (TLR) 3 or TLR4, and then induces p38 target genes, including cathepsin K (CTSK), S100 calcium binding protein A8 (S100A8), matrix metalloproteases (MMP)8, and MMP14, and potentially contributes to plaque complications, such as aneurysm formation and plaque disruption [7].