HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation

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Sci. Signal.  11 Aug 2015:
Vol. 8, Issue 389, pp. ra79
DOI: 10.1126/scisignal.aaa2581

Maintaining vascular health with HDL

Flow through blood vessels subjects endothelial cells to abnormal shear forces at specific locations that trigger inflammation, which contributes to atherosclerotic plaque formation. Galvani et al. found that vascular inflammation and atherosclerosis in mice were suppressed by the endothelial cell receptor S1P1, which is activated by S1P, a lipid mediator that is abundant in blood bound to different chaperone proteins. S1P suppressed inflammation in cultured endothelial cells when bound to the lipoprotein ApoM+HDL. Thus, S1P bound to different chaperones triggered distinct or “biased” signaling pathways, which may also contribute to the protective effect of HDL, commonly called “good cholesterol,” in atherosclerosis.