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Contents 1 Sphingomyelin Synthesis in Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Sphingomyelin and Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Plasma Sphingomyelin and Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Membrane Sphingomyelin and Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Sphingosine-1-Phosphate and Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract Atherosclerosis is the major cause of mortality in the developed countries. Although presently known risk factors have some predictive value for the disease, a major part of the variability in this process remains unexplained. It is extremely important to find new approaches for better understanding of the disease and for treating it. Exploration of the sphingolipid metabolism is one of these approaches. Sphingolipids are a large class of lipids with structural and signaling functions. Recent researches indicated that these lipids play important roles in the development of atherosclerosis. In this chapter, we summarized the major findings in the field. Keywords Sphingolipid • Sphingomyelin • Ceramide • Sphingosine-1-phosphate • Atherosclerosis

X.-C. Jiang (*) • J. Liu Department of Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave. Box 5, Brooklyn, NY 11203, USA Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, NY 11209, USA e-mail: [email protected] E. Gulbins and I. Petrache (eds.), Sphingolipids in Disease, Handbook of Experimental Pharmacology 216, DOI 10.1007/978-3-7091-1511-4_7, # Springer-Verlag Wien 2013

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X.-C. Jiang and J. Liu

1 Sphingomyelin Synthesis in Atherosclerosis Sphingomyelin synthesis is a major pathway of ceramide conversion. This is accomplished by sphingomyelin synthase (SMS) enzymes. SMS gene family consists of three members, SMS1-, SMS2-, and SMS-related protein (SMSr). SMS1 is found in the trans-Golgi complex, while SMS2 is predominantly found in the plasma membranes (Huitema et al. 2004; Yamaoka et al. 2004). SMSr, the third member of the gene family, has no SMS activity but catalyzes the synthesis of ceramide-phosphoethanolamine in the ER lumen (Huitema et al. 2004; Vacaru et al. 2009). SMS1 and SMS2 activity are coexpressed in a variety of tissues and cells with different ratios. SMS1 is the major SMS in macrophages (Li et al. 2012), while SMS2 is the major o