This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tabas, I. Search for Related Content PubMed PubMed Citation Articles by Tabas, I. Related Collections Lipid and lipoprotein metabolism Related Article

(Circulation. 2004;110:3400-3401.)
© 2004 American Heart Association, Inc.

Editorial

Sphingolipids and Atherosclerosis

A Mechanistic Connection? A Therapeutic Opportunity?

Ira Tabas, MD, PhD

From the Departments of Medicine, Anatomy and Cell Biology, and Physiology and Cellular Biophysics, Columbia University, New York.

Correspondence to Ira Tabas, MD, PhD, Department of Medicine, Columbia University, New York, NY 10032. E-mail iat1@columbia.edu

Key Words: Editorials • sphingomyelins • ceramides • atherosclerosis • lipoproteins

An extract of the first 250 words of the full text is provided, because this article has no abstract.

When inhibitors of biochemical pathways are fed to experimental animals, the goals are to understand physiological or pathophysiological consequences of the inhibited pathway and possibly to obtain evidence for new therapeutic strategies for diseases affected by the pathway. In this issue of Circulation, Park et al¹ fed Apoe^–/– mice a compound isolated from fungi, myriocin, that inhibits the rate-limiting enzyme in ceramide and sphingolipid biosynthesis, serine palmitoyl transferase (SPT). The study was founded on a series of previous observations that implicated sphingomyelin (SM) and ceramide in lipoprotein metabolism and atherosclerosis, including a study showing that plasma SM is an independent risk factor for coronary artery disease in humans.² The goal of the study by Park et al¹ was to test the effect of myriocin on plasma lipoprotein levels and atherogenesis in a well-defined animal model of atherosclerosis. The authors found that myriocin treatment in Apoe^–/– mice was associated with a protective lipoprotein profile—namely, a decrease in ßVLDL and LDL, an increase in HDL, and a reduction in atherosclerosis.

See p 3465

What can we learn from these results in terms of mechanism and therapeutic potential? With regard to mechanism, two crucial issues are the specificity of myriocin and the distinction between primary lipoprotein versus primary arterial-wall mechanisms. As the authors point out, myriocin may have effects that are independent of its ability to inhibit SPT, such as an immunosuppressive action.³ Given the role of immunologic processes in atherogenesis,⁴ one needs to consider the possibility that this effect of the . . . [Full Text of this Article]

Related Article:

Inhibition of Sphingomyelin Synthesis Reduces Atherogenesis in Apolipoprotein E–Knockout Mice

Tae-Sik Park, Robert L. Panek, Sandra Bak Mueller, Jeffrey C. Hanselman, Wendy S. Rosebury, Andrew W. Robertson, Erick K. Kindt, Reynold Homan, Sotirios K. Karathanasis, and Mark D. Rekhter
Circulation 2004 110: 3465-3471. [Abstract] [Full Text]

This article has been cited by other articles:

				S. T. Pruett, A. Bushnev, K. Hagedorn, M. Adiga, C. A. Haynes, M. C. Sullards, D. C. Liotta, and A. H. Merrill Jr. Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases ("sphingosines") and related amino alcohols J. Lipid Res., August 1, 2008; 49(8): 1621 - 1639. [Abstract] [Full Text] [PDF]

				J. C. Nelson, X.-C. Jiang, I. Tabas, A. Tall, and S. Shea Plasma Sphingomyelin and Subclinical Atherosclerosis: Findings from the Multi-Ethnic Study of Atherosclerosis Am. J. Epidemiol., May 15, 2006; 163(10): 903 - 912. [Abstract] [Full Text] [PDF]

				C. Y. Lee, A. Lesimple, M. Denis, J. Vincent, A. Larsen, O. Mamer, L. Krimbou, J. Genest, and M. Marcil Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B J. Lipid Res., March 1, 2006; 47(3): 622 - 632. [Abstract] [Full Text] [PDF]

				A. Nilsson and R.-D. Duan Absorption and lipoprotein transport of sphingomyelin J. Lipid Res., January 1, 2006; 47(1): 154 - 171. [Abstract] [Full Text] [PDF]