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Figure 2. Endothelial-derived and incoming exosomes mediate vascular inflammation and immune cell activation in atherosclerosis. Exosomes released by endothelial cells influence the function of multiple immune and vascular cells. Endothelial cells secrete exosomes that activate the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) pathway, promoting proinflammatory M1 polarization in macrophages. Exosomal miR-155 inhibits Kruppel-like factor 2 (KLF2), and miR-92a suppresses Kruppel-like factor 4 (KLF4), enhancing low-density lipoprotein (LDL) uptake. The long non-coding RNA LINC01005 acts as a sponge for miR-128-3p, indirectly increasing KLF4 expression and contributing to atherosclerosis progression. Exosomes derived from endothelial cells also modulate neutrophil activation. miR-505 inhibits sirtuin 3 (SIRT3), leading to elevated reactive oxygen species (ROS) and enhanced neutrophil extracellular trap (NET) release. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), delivered by endothelial exosomes, also promotes NET formation. In the reverse direction, macrophage-derived exosomal miR-4532 targets specificity protein 1 (SP1) in endothelial cells, activating NF-κB subunit p65 and upregulating intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1), thereby promoting leukocyte adhesion. Exosomes from neutrophils and perivascular adipose tissue (PVAT) exacerbate endothelial injury. In contrast, mesenchymal stem cell (MSC)-derived exosomes protect endothelial cells by inhibiting caspase-3-mediated apoptosis, reducing oxidative stress, and restoring redox balance. Created using https://BioRender.com.