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Xu W, Wei Z, Dong J, et al. Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells. Front Pharmacol. 2017;8:586doi: 10.3389/fphar.2017.00586.
Xu, W., Wei, Z., Dong, J., Duan, F., Chen, K., Chen, C., Liu, J., Yang, X., Chen, L., Xiao, H., & Liu, A. (2017). Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells. Frontiers in pharmacology, 8586. https://doi.org/10.3389/fphar.2017.00586
Xu, Wenjuan, et al. "Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells." Frontiers in pharmacology vol. 8 (2017): 586. doi: https://doi.org/10.3389/fphar.2017.00586
Xu W, Wei Z, Dong J, Duan F, Chen K, Chen C, Liu J, Yang X, Chen L, Xiao H, Liu A. Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells. Front Pharmacol. 2017 Aug 31;8:586. doi: 10.3389/fphar.2017.00586. eCollection 2017. PMID: 28912717; PMCID: PMC5583968.
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Front Pharmacol. 2017 Aug 31;8:586. doi: 10.3389/fphar.2017.00586. eCollection 2017.

Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells.

Frontiers in pharmacology

Wenjuan Xu, Ziyi Wei, Jiaojiao Dong, Feipeng Duan, Kuikui Chen, Chang Chen, Jie Liu, Xiaowei Yang, Lianming Chen, Hongbin Xiao, An Liu

Affiliations

  1. Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesBeijing, China.
  2. School of Chinese Materia Medica, Beijing University of Chinese MedicineBeijing, China.

PMID: 28912717 PMCID: PMC5583968 DOI: 10.3389/fphar.2017.00586

Abstract

Atherosclerosis (AS) is a chronic disorder of large arteries that is a major risk factors of high morbidity and mortality. Oxidative modification LDL is one of the important contributors to atherogenesis. Macrophages take up ox-LDL and convert into foam cells, which is the hallmark of AS. To advance the understanding of the metabolic perturbation involved in ox-LDL induced macrophage-derived foam cells and discover the potential biomarkers of early AS, a global metabolomics approach was applied based on UHPLC-QTOF/MS. Multivariate statistical analyses identified five metabolites (25-azacholesterol, anandamide, glycocholate, oleoyl ethanolamide, and 3-oxo-4, 6-choladienoate) for distinguishing foamy macrophages from controls. Among the six main metabolic pathways, the unsaturated fatty acid, especially arachidonic acid metabolism, contributed importantly to early AS. A new biomarker, anandamide (AEA), whose synthesis and metabolism in macrophages are disturbed by overloaded ox-LDL, results in metabolic obstruction. This study is the first to investigate the metabolic disturbance in macrophage-derived foam cells induced by ox-LDL and screen potential biomarkers and metabolic pathways associated with early AS. Our findings provide a new insight in the underlying pathophysiological mechanisms and also help to identify novel targets for the intervention of AS.

Keywords: anandamide over-accumulation; atherosclerosis; macrophage-derived foam cells; metabolomics; oxidized-LDL

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