Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis

作者：Shuanhu Li, Xin Zhou, Qinchun Duan, Shukun Niu, Peng‐Quan Li, Yihan Feng, Ye Zhang, Xuehong Xu, Shouping Gong, Huiling Cao · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26073252 · 被引用次数：11 · 研究领域：Autophagy in Disease and Therapy、Inflammasome and immune disorders、Immune cells in cancer

Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation and immune cell infiltration, is linked to plaque formation and cardiovascular events. While traditionally associated with lipid metabolism and endothelial dysfunction, recent research highlights the roles of autophagy and clonal hematopoiesis (CH) in its pathogenesis. Autophagy, a cellular process crucial for degrading damaged components, regulates macrophage homeostasis and inflammation, both of which are pivotal in atherosclerosis. In macrophages, autophagy influences lipid metabolism, cytokine regulation, and oxidative stress, helping to prevent plaque instability. Defective autophagy exacerbates inflammation, impairs cholesterol efflux, and accelerates disease progression. Additionally, autophagic processes in endothelial cells and smooth muscle cells further contribute to atherosclerotic pathology. Recent studies also emphasize the interplay between autophagy and CH, wherein somatic mutations in genes like TET2, JAK2, and DNMT3A drive immune cell expansion and enhance inflammatory responses in atherosclerotic plaques. These mutations modify macrophage function, intensifying the inflammatory environment and accelerating atherosclerosis. Chaperone-mediated autophagy (CMA), a selective form of autophagy, also plays a critical role in regulating macrophage inflammation by degrading pro-inflammatory cytokines and oxidized low-density lipoprotein (ox-LDL). Impaired CMA activity leads to the ac...