赖氨酸乙酰转移酶2B/干扰素调节因子7/C-C基序趋化因子配体5在动脉粥样硬化中调控巨噬细胞极化的研究现状OA

Atherosclerosis(AS)is a complex cardiovascular disease triggered by chronic inflammation and serves as a critical pathological basis for the development and progression of numerous cardiovascular and cerebrovascular diseases.Its pathogenesis is intricate,which involvs various cells and molecules.In the progression of atherosclerosis,macrophages,as key players in both innate and adaptive immune responses,play a pivotal role in the progression of the disease through their polarization states.In recent years,a growing body of research has focused on the regulatory mechanisms underlying the functional and phenotypic swiching of macrophages.Among these,the lysine acetyltransferase 2B(KAT2B)/interferon regulatory factor 7(IRF7)/C-C motif chemokine ligand 5(CCL5)signaling axis has been demonstrated to play a significant role in regulating macrophage polarization,gradually becoming a hotspot in this field.Studies have found that KAT2B can specifically enhance the transcriptional activity of the transcription factor IRF7,and the activated IRF7 further acts as a molecular switch to initiate the downstream key chemokine CCL5,thereby regulating the robust expression of CCL5.As a potent pro-inflammatory chemokine,CCL5 triggers the infiltration of a large number of macrophages.These macrophages release a spectrum of pro-inflammatory cytokines in the inflammatory microenvironment,exacerbating local inflammatory cascade,promoting the polarization of macrophages toward the pro-inflammatory M1 phenotype,and ultimately accelerating the progression of AS.In summary,the KAT2B-IRF7-CCL5 signaling pathway plays an important role in the pathophysiological process of AS,ultimately influencing the polarization fate of macrophages.Although existing studies have preliminarily elucidated the significance of this signaling axis,the precise upstream activation signals,its interactions with other signaling pathways,and the potential translational value of targeting this axis for novel therapeutic strategies still require more in-depth and systematic exploration.This article aims to discuss the molecular mechanisms of KAT2B-IRF7-CCL5 and the latest research progress in its regulation of macrophage polarization in atherosclerosis,providing novel insights for future therapeutic strategies for AS.