FIG. 6.

S100A8/A9, ROS, and NETs contribute to atherosclerosis and thrombosis. S100A8/A9 increases the expression of ICAM-1 and VCAM-1 on the vascular endothelium. S100A8/A9-augmented platelets interact with leukocytes to activate them and induce expression of the ICAM-1 binding molecule Mac-1. S100A8/A9 through a TLR4-mediated pathway can increase Mac-1 and ICAM-1 binding. Once bound the leukocytes can extravasate through the endothelium that has been made more permeable by ROS and S100A8/A9. The leukocytes, specifically monocytes, mature into macrophages and then foam cells through the uptake of low-density lipoproteins, leading to atherogenesis. Neutrophil NETs contribute to thrombogenesis through sequestering platelets in the DNA, aiding in clot formation. The platelets, activated by NETs, secrete CXCL4 and CCR5, activating more neutrophils and encouraging NETosis. CCR5, C-C chemokine receptor type 5; CXCL4, chemokine (C-X-C motif) ligand 4; ICAM-1, intracellular adhesion molecule 1; LDLs, low-density lipoproteins; Mac-1, macrophage-1 antigen; VCAM-1, vascular adhesion molecule 1. Color images are available online.