S100A8 and S100A9: DAMPs at the Crossroads between Innate Immunity, Traditional Risk Factors, and Cardiovascular Disease

Figure 1

Overview of the interplay between S100A8/A9, traditional CV risk factors, circulating phagocytes, and atherogenesis. Smoking, hyperlipidemia, hyperglycemia, and obesity induce elevated S100A8/A9 production either directly or indirectly by stimulating neutrophilia and monocytosis. S100A8/A9 enhances phagocyte production in the bone marrow and facilitates their recruitment into the vascular wall through endothelial activation and increased Mac-1 expression and affinity. These effects are primarily mediated by RAGE and accelerated by hyperglycemia. In the vascular wall, S100A8/A9 binding to TLR4 triggers phagocyte activation and secretion of inflammatory cytokines, further contributing to phagocyte recruitment and accelerated atherogenesis. M-CSF: macrophage colony stimulating factor; GM-CSF: granulocyte-macrophage colony stimulating factor; RAGE: receptor for advanced glycation end products; TLR4: toll-like receptor 4.