The role of sphingolipids in endothelial barrier function.

Sphingolipids are a ubiquitous family of essential lipids with an increasingly understood role as biologically active mediators in numerous physiologic and pathologic processes. Two particular sphingolipid species, sphingosine-1-phosphate and ceramide, and their metabolites interact both directly and indirectly with endothelial cells to regulate vascular permeability. Sphingosine-1-phosphate generally augments endothelial integrity while ceramide tends to promote vascular leak, and a tight balance between the two is necessary to maintain normal physiologic function. The mechanisms by which sphingolipids regulate endothelial barrier function are complex and occur through multiple different pathways, and disruptions or imbalances in these pathways have been implicated in a number of specific disease processes. With improved understanding of sphingolipid biology, endothelial function, and the interactions between the two, several targets for therapeutic intervention have emerged and there is immense potential for further advancement in this field.