Song Jae-Hwi, Kim Goon-Tae, Park Kyung-Ho, Park Woo-Jae, Park Tae-Sik
Department of Life Science, Gachon University, Sungnam 13120, Republic of Korea.
Department of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea.
Biomol Ther (Seoul). 2021 Jul 1;29(4):373-383. doi: 10.4062/biomolther.2020.218.
Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.
动脉粥样硬化是指斑块在主要动脉中的沉积。它是一种炎症性疾病，涉及巨噬细胞和各种脂质（低密度脂蛋白[LDL]胆固醇、神经酰胺、1-磷酸鞘氨醇[S1P]）的积累。此外，内皮细胞、巨噬细胞、白细胞和平滑肌细胞是动脉粥样硬化形成过程中的主要参与者。鞘脂现在正成为包括动脉粥样硬化形成过程在内的各种病理生理过程中的重要调节因子。存在多种鞘脂，如神经酰胺、1-磷酸神经酰胺、鞘氨醇、二氢鞘氨醇、1-磷酸鞘氨醇（S1P）、鞘磷脂和数百种糖鞘脂。其中，神经酰胺、糖鞘脂和S1P在动脉粥样硬化形成过程中起重要作用。动脉粥样硬化斑块含有较高含量的神经酰胺、糖鞘脂和鞘磷脂。抑制从头合成神经酰胺可减少动脉粥样硬化的发展。S1P通过与S1P受体（S1PR）结合来调节动脉粥样硬化的发生。在五种S1PR（S1PR1 - 5）中，S1PR1和S1PR3主要发挥抗动脉粥样硬化的特性。本综述主要关注神经酰胺和S1P通过S1PR在动脉粥样硬化发展过程中的作用。此外，还讨论了动脉粥样硬化方面的最新研究结果和潜在的治疗意义。
