Abstract

The aberrant deposition of lipid droplets (LDs) is a pivotal feature in foam cells formation and has significant implications for understanding the pathogenesis and early diagnosis of atherosclerosis (AS). In this study, we engineered a fluorescent probe, PyTPA-LD, for the reliable tracking of intracellular LDs. Through the application of PyTPA-LD, we monitored LD generation during the transition of macrophages induced by oxidized low-density lipoprotein (ox-LDL) into foam cells. Furthermore, we observed dynamic changes in lysosomes and LDs during lipophagy in this transitional process. Our study unveiled the dual role of lysosomes in LD formation: the degradation and release of ox-LDL within lysosomes promote LDs formation, while concurrently, lipophagy contributes to LDs clearance. This novel perspective provides a comprehensive understanding of the dynamic generation and clearance of LDs during foam cells formation. This work offers crucial insights into the pathogenic mechanisms underlying AS, deepening our understanding of AS development and providing valuable insights into lipid metabolism-related diseases.

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