High-density lipoprotein, sphingosine 1-phosphate, and atherosclerosis

Numerous epidemiologic and interventional studies have revealed an inverse relationship between plasma concentrations of high-density lipoprotein (HDL) and coronary risk. There are several well-documented HDL functions, which may account for the antiatherogenic effects of this lipoprotein. Recent studies document that HDL serves as a carrier for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P), which determines its functional properties. Generally available databases (eg, PubMed) were used, as well as our own results. An increasing body of evidence indicates that S1P is a mediator of many of the atheroprotective effects of HDL, including the ability to promote vasodilation and angiogenesis and protection against ischemia/reperfusion injury. These latter effects are believed to involve S1P-mediated retardation or suppression of inflammatory processes, such as endothelial expression of adhesion molecules, production of proinflammatory chemokines and cytokines, generation of reactive oxygen species, and cardiomyocyte apoptosis after myocardial infarction. This review article summarizes the evidence that S1P is a component of HDL contributing to the antiatherogenic and cardioprotective potential attributed to this lipoprotein.