HDL quality or cholesterol cargo: what really matters--spotlight on sphingosine-1-phosphate-rich HDL.

The absolute level of HDL cholesterol (HDL-C) may not be the only criterion contributing to their antiatherothrombotic effects. This review focuses on evidence in support of the concept that HDL-bound sphingosine-1-phosphate (S1P) plays a role in different HDL atheroprotective properties and may represent a potential target for therapeutic interventions. Recent large randomized clinical trials testing the hypothesis of raising HDL-C with niacin and dalcetrapib in statin-treated patients failed to improve cardiovascular outcomes. Emerging evidence suggests that many of the cardioprotective functions of HDL, such as vasodilation, angiogenesis and endothelial barrier function, protection against ischemia/reperfusion injury, and inhibition of atherosclerosis, may be attributable to its S1P cargo. HDL-associated S1P may represent a future therapeutic target. HDL functionality is affected by its composition and there is evidence to suggest S1P plays a role in some of HDL's functions and atheroprotective properties.