Seo Jae Won, Park Kyu Seong, Lee Gwang Bin, Park Sang-Eun, Choi Jae-Hoon, Moon Myeong Hee
Department of Chemistry, Yonsei University, Seoul 03722, Korea.
Department of Life Science, Research Institute for Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.
Immune Netw. 2023 Jun 15;23(4):e28. doi: 10.4110/in.2023.23.e28. eCollection 2023 Aug.
Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including and were markedly increased but expressions of and related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.
巨噬细胞中的脂质积累是动脉粥样硬化中观察到的一个突出现象。此前，内膜泡沫巨噬细胞（FM）与内膜非泡沫巨噬细胞（NFM）相比，炎症基因表达降低。由于巨噬细胞中脂质代谢的重编程会影响免疫功能，因此内膜巨噬细胞的脂质谱分析对于理解动脉粥样硬化病变中巨噬细胞的表型变化似乎很重要。虽然已经在动脉粥样硬化主动脉组织和培养的巨噬细胞中进行了脂质组学分析，但尚未对来自动脉粥样硬化主动脉的原代主动脉巨噬细胞进行直接脂质谱分析。我们利用纳流超高效液相色谱-串联质谱法提供了来自小鼠主动脉的内膜非泡沫和泡沫巨噬细胞以及外膜巨噬细胞的全面脂质谱。我们还分析了与脂质代谢相关的每种巨噬细胞类型的基因表达。FM中脂肪酸、胆固醇酯、磷脂酰胆碱、溶血磷脂酰胆碱、磷脂酰肌醇和鞘磷脂水平升高。然而，与NFM相比，FM中磷脂酰乙醇胺、磷脂酸和神经酰胺水平降低。有趣的是，FM中三酰甘油（TG）水平降低。FM中包括 和 在内的脂解相关基因的表达明显增加，但与TG合成相关的 和 的表达降低。转录组和脂质组数据分析揭示了主动脉巨噬细胞中每种脂质代谢途径调控的差异。这些全面的脂质组学数据可以阐明动脉粥样硬化主动脉中巨噬细胞的表型。
