Department of Internal Medicine (463) and Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115, Bonn, Germany.
Semin Immunopathol. 2018 Feb;40(2):203-214. doi: 10.1007/s00281-017-0656-7. Epub 2017 Oct 2.
Atherosclerosis is characterized by chronic low grade inflammation of arteries that results in the development of lipid dense plaques. Chronic inflammation induced by Western-type diet is associated with the risk of developing atherosclerosis, and new insights shed light on the importance of metabolic and functional reprogramming in monocytes and macrophages for progression of atherosclerosis. This review aims to provide an overview of our current understanding into how the metabolic reprogramming of glucose, cholesterol, fatty acid, and amino acid metabolism in macrophages contributes to inflammation during atherosclerosis. Recent insights suggest that transcriptional and epigenetic adaptation within innate immune cells (termed trained immunity) play an important role in the pathogenesis of atherosclerosis. We propose that metabolic changes induced by pro-atherogenic lipoproteins partly mediate these changes in trained macrophages. Finally, we discuss the possibility of manipulating cellular metabolism of immune cells for targeted therapeutic intervention against atherosclerosis.
动脉粥样硬化的特征是动脉的慢性低度炎症，导致脂质密集斑块的形成。西方饮食诱导的慢性炎症与动脉粥样硬化发病风险相关，新的研究结果提示代谢和功能重编程在单核细胞和巨噬细胞中对动脉粥样硬化进展的重要性。本综述旨在概述我们目前对巨噬细胞中葡萄糖、胆固醇、脂肪酸和氨基酸代谢的代谢重编程如何促进动脉粥样硬化炎症的理解。最近的研究结果表明，固有免疫细胞（称为训练有素的免疫）内的转录和表观遗传适应在动脉粥样硬化发病机制中发挥重要作用。我们提出，由致动脉粥样硬化脂蛋白诱导的代谢变化部分介导了训练有素的巨噬细胞中的这些变化。最后，我们讨论了操纵免疫细胞的细胞代谢以针对动脉粥样硬化进行靶向治疗干预的可能性。
