Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.218
Bioactive Sphingolipids as Major Regulators of Coronary Artery Disease
Jae-Hwi Song1,†, Goon-Tae Kim1,†, Kyung-Ho Park2, Woo-Jae Park3,* and Tae-Sik Park1,*
1Department of Life Science, Gachon University, Sungnam 13120,
2Department of Nutrition, Hallym University, Chuncheon 24252,
3Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
*E-mail:ooze@gachon.ac.kr (Park WJ),tspark@gachon.ac.kr (Park TS)
Tel: +82-32-899-6417 (Park WJ), +82-31-750-8824 (Park TS)
Fax: +82-32-899-5678 (Park WJ), +82-31-750-8573 (Park TS)
The first two authors contributed equally to this work.
Received: December 3, 2020; Revised: January 4, 2021; Accepted: January 6, 2021; Published online: April 27, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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.
Keywords: Sphingolipid, Ceramide, Sphingosine 1-phosphate, Sphingosine-1-phosphate receptor, Atherosclerosis


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