Vascular effects of sphingolipids

The sphingomyelin metabolites ceramide, sphingosine 1‐phosphate (S1P) and sphingosylphosphorylcholine (SPC) are emerging modulators of vascular tone. While ceramide appears to act primarily intracellularly, S1P and SPC appear to mainly work via specific receptors, although those for SPC have not yet been defined unequivocally. Each of the sphingomyelin metabolites can induce both vasoconstriction and vasodilatation and, in some cases – ceramide on the one hand, and S1P and SPC on the other hand – have opposite effects on vascular tone. The differences in effects between vessels may relate to the relative roles of endothelial and smooth muscle cells in mediating them, as well as to the distinct expression patterns of S1P receptors among vascular beds and among endothelial and smooth muscle cells. Recent evidence suggests that vascular tone is not only modulated by sphingomyelin metabolites which are exogenously added or reach the vessel wall via the bloodstream but also by those formed locally by cells in the vessel wall. Such local formation can be induced by known vasoactive agents such as angiotensin II and may serve a signalling function. Conclusion: We conclude that sphingomyelin metabolites are important endogenous modulators of vascular function, which may contribute to the pathophysiology of some diseases and be targets for therapeutic interventions.