Fig. 5

Regulatory mechanisms of macrophages in aneurysm. Macrophages mainly regulate inflammatory response, ECM remodeling and VSMC apoptosis in AA. Macrophages clear apoptotic VSMCs through phagocytosis and produce large amounts of ROS, which further activate macrophages. Macrophages can also secrete pro-inflammatory cytokines (such as IL-6, TNF, IL-1β), chemokines (such as CXCL1 and CCL2) and ANGPTL2 to promote the development of inflammation. On the contrary, macrophages also secrete anti-inflammatory factors such as IL-10 and TGF-β by upregulating the transcription factor KLF6 or downregulating the activation of PPARδ. In addition, macrophages release proteinases such as MMP-9, MMP-2, and MMP-3 by activating the STING, TERT, JNK and p38 pathways, leading to aortic wall bleeding and rupture. In turn, macrophage recruitment, accumulation, proliferation, and activation are modulated by microenvironmental conditions (such as hemodynamics, circumferential stress, PVAT and ILT). (Created with BioRender.com)