ABSTRACT
AIM:To explore the role of sphingosine 1-phosphate (S1P) in the dysfunction of vascular endo-thelial cells exposed to high glucose.METHODS: In human aortic endothelial cells cultured under high-glucose ( 22 mmol/L glucose) medium, nitric oxide ( NO) level, polymorphonuclear neutrophil-endothelial cell adhesion rate, protein level of intercellular adhesion molecule-1 ( ICAM-1) , migration of endothelial cells and Akt/endothelial nitric oxide syn-thase ( eNOS) pathway activation were observed after S1P, sphingosine kinase-1 inhibitor and/or Akt inhibitor treatments. RESULTS:S1P decreased NO level, increased polymorphonuclear neutrophil adhesive rate, enhanced ICAM-1 protein level, and inhibited migration of endothelial cells and activation of Akt/eNOS pathway in endothelial cells cultured under high-glucose condition.Sphingosine kinase-1 inhibitor, which reduced S1P content, significantly improved the above endo-thelial cell function indexes and restored the activation of Akt/eNOS pathway.CONCLUSION: S1P promoted high glu-cose-induced dysfunction of endothelial cells probably by inhibiting the activation of Akt/eNOS signal pathway.Targeting S1P is expected to become one of potential treatment strategies to reduce endothelial cell dysfunction.