Implication of sphingosin-1-phosphate in cardiovascular regulation

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by phosphorylation of sphingosine catalyzed by sphingosine kinase. S1P acts mainly through its high affinity G-protein-coupled receptors and participates in the regulation of multiple systems, including cardiovascular system. It has been shown that S1P signaling is involved in the regulation of cardiac chronotropy and inotropy and contributes to cardioprotection as well as cardiac remodeling; S1P signaling regulates vascular function, such as vascular tone and endothelial barrier, and possesses an anti-atherosclerotic effect; S1P signaling is also implicated in the regulation of blood pressure. Therefore, manipulation of S1P signaling may offer novel therapeutic approaches to cardiovascular diseases. As several S1P receptor modulators and sphingosine kinase inhibitors have been approved or under clinical trials for the treatment of other diseases, it may expedite the test and implementation of these S1P-based drugs in cardiovascular diseases.

Increase in circulating sphingosine-1-phosphate and decrease in ceramide levels in psoriatic patients

“…It was found to be the key regulator of lymphocyte trafficking, endothelial barrier function and vascular tone. In pathology, S1P metabolism is associated with inflammatory and autoimmune diseases: rheumatoid arthritis [ 23 ], multiple sclerosis [ 41 ] and cardiovascular diseases [ 27 ].…”

Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis

“…Other functions of S1P signaling in the heart, including chronotropic and inotropic effects, have been comprehensively reviewed elsewhere[83, 92]. To date only few studies in vitro suggested a pro-hypertrophic function for S1P on CM through S1PR1 [93, 94], while the role of S1P signaling in pathological cardiac hypertrophy (PCH) induced by pressure overload is virtually unexplored.…”

Effect of Sphingosine-1-Phosphate on Intracellular Free Ca2+ in Cat Esophageal Smooth Muscle Cells

“…Similar abolishment was observed for nimodipine, suggesting that Ca 2+ influx from the extracellular environment occurs via L-type Ca 2+ channels in cat esophageal smooth muscle cells. While S1P effects on renovascular cells were fully blocked by chelation of extracellular Ca 2+ and inhibited by Ca 2+ entry blockers ( Li and Zhang, 2016 ), incubation with the Ca 2+ -channel blocker nimodipine partially reduced the S1P-evoked increase in [Ca 2+ ] i in esophageal smooth muscle cells. The discrepancy in these results may be related to differences in the cell types employed in these studies.…”