Untargeted Lipidomics Reveals Lipid Metabolism Dysfunction During Macrophage Foaming

doi:10.7503/cjcu20240053

Abstract

Abstract:

Atherosclerosis is a multifactorial chronic complex disease characterized by the accumulation of lipids， inflammatory responses， and ultimately fibrous plaque formation within arterial walls. Plaque formation begins with the abnormal accumulation of lipids engulfed by macrophages within arterial walls， forming so-called foam cells. Despite the pivotal role of foam cell formation in the pathophysiological remodeling process of blood vessels， in-depth research into lipid metabolism disturbances during macrophage foam cell formation is still relatively lacking. In this study， we constructed and optimized a lipidomics analysis workflow， applying it to analyzing metabolic reprogramming during macrophage foam cell formation. A total of 645 lipid molecules belonging to 16 lipid subclasses were identified. Principal component analysis， time-series pattern analysis， and volcano plot analysis revealed significant differences in lipid levels at different stages of foam cell formation. As incubation time with oxidized low-density lipoprotein increased， the degree of lipid metabolism dysfunction in foam cells increased. Triglycerides， hemolytic phospholipids， and ether phospholipids were upregulated， while phosphatidylserine was downregulated. The significant accumulation of triglycerides enhanced the inflammatory response of macrophages， promoting foam cell formation by further engulfing oxidized low-density lipoprotein. Meanwhile， the synthesis of phosphatidylserine and hemolytic phosphatidylcholine increased significantly in the late stages of foam cell formation， indicating a positive correlation between foam cell formation and cell apoptosis. These lipid molecules may serve as signaling molecules to attract macrophages for the clearance of apoptotic cells. This study not only reveals the significant upregulation of inflammatory responses during foam cell formation but also elucidates the close connection between lipid metabolism disturbances and cell apoptosis signaling.

Key words: Macrophage, Cell foaming, Lipidomics, Inflammation, Apoptosis

CLC Number:

O657

TrendMD:

WANG Zengyu, LIU Baohong, QIAO Liang, LIN Ling. Untargeted Lipidomics Reveals Lipid Metabolism Dysfunction During Macrophage Foaming[J]. Chem. J. Chinese Universities, 2024, 45(11): 20240053.

Figures/Tables 7

References 25

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