Sphingolipids and vascular tone regulation

From LipidomicsWiki

Jump to: navigation, search
Atherosclerosis is associated with endothelial dysfunction such as impaired release of nitric oxide (NO) and as a consequence, promotion of vasoconstriction. Sphingolipids have been shown to have a relaxing role in SMC physiology and ceramide was documented to decrease the rate of intracellular calcium mobilization (Johns et al. 1999). Ceramide and endothelium-derived NO commonly promote the relaxation of rat endothelial-intact aortic rings (Jin et al. 1999). Sphingomyelin signalling through a nitric oxide-dependent mechanism may have an important role in vascular tone regulation. Another sphingomyelin pathway metabolite, sphingosine, opposes effects of ceramide and induces vasoconstriction in porcine coronary arteries (Murohara et al. 1996).Thus, sphingosine impairs endothelial function by blocking endothelium-dependent relaxation. S1P has been documented to regulate vascular tone acting directly on VSMCs or indirectly by stimulating the release of vasoactive substances such as NO from endothelial cells (Igarashi and Michel, 2000). The signalling pathway may involve activation of the S1P1 receptor, followed by activation of PI-3 kinase and protein kinase B/Akt and Akt-mediated phosphorylation of e-NOS (Igarashi et al. 2001, Morales-Ruiz et al. 2001). The effect of S1P was investigated in rat microvessels (Bischoff et al. 2000). S1P caused a transient increase in intracellular Ca++ levels and vasoconstriction of isolated vessels. This effect may happen due to signalling via G protein receptors coupled to a pertussis toxinsensitive G protein. The mechanism of ceramide-induced vasodilation is still unclear, however protein kinase C (PKC) has emerged as a putative candidate downstream effector for ceramide (Lee et al. 1996).


Other pages in this category:



Personal tools
Create a book