Sphingomyelin metabolites in vascular cell signaling and atherogenesis

The atherosclerotic lesion most probably develops through a number of cellu lar events which implicate all vascular cell types and include synthesis of extracellular proteins, cell proliferation, differentiation and death. Sph ingolipids and sphingolipid metabolizing enzymes may play important roles i n atherogenesis, not only because of lipoprotein alterations but also by me diating a number of cellular events which are believed to be crucial in the development of the vascular lesions such as proliferation or cell death. E xogenous sphingolipids may mediate various biological effects such as apopt osis, mitogenesis or differentiation depending on the cell type. Moreover, several molecules present in the atherogenic lesion, such as oxidized LDL, growth factors or cytokines, which activate intracellular signaling pathway s leading to vascular cell modifications, can stimulate sphingomyelin hydro lysis and generation of ceramide (and other metabolites as sphingosine-1-ph osphate). Here we review the potential implication of the sphingomyelin/cer amide cycle in vascular cell signaling related to atherosclerosis, and more generally the role of sphingolipids in the events observed during the athe rosclerotic process as cell differentiation, migration, adhesion, retractio n, proliferation and death. (C) 2000 Elsevier Science Ltd. All rights reser ved.