Fig. 2

Overview of inflammatory responses in atherosclerotic development. At the early stages, activated platelets mediate firm adhesion between platelets, leukocytes, and the vascular endothelium by secreting platelet-activating factor (PAF). In progressing plaques, VSMCs migrate from the medial to the subendothelial space where they undergo proliferation and developing fibrous cap. OxLDL induces phenotype switching of VSMCs to synthetic, macrophage-like VSMCs and the formation of foam cells. Excessive deposition of lipids triggers VSMC apoptosis and senescence, leading to necrosis. At predilection sites with the disturbed flow, neutrophil-released neutrophil extracellular traps (NETs) induce desquamation of endothelial cells and lead to rapid occlusion of the affected vessels. Monocyte-derived macrophages ingest oxLDL and release pro-inflammatory cytokines. Excessive deposition of lipids, as well as cytokines and histamine released from dendritic cells and mast cells, trigger the proliferation, polarization of macrophages, or even cell death