Activation of intracellular signaling systems by high-density lipoproteins

The proteosome of high-density lipoprotein particles is quite complex and consists of up to 75 different proteins and enzymes. The specific protein cargo of HDL particles regulates their functionality. In addition to their documented capacity to engage in reverse cholesterol transport, reduce oxidized lipid, and function as apoprotein donors, HDL particles can activate a variety of signaling systems in endothelial cells, smooth muscle cells, and platelets. The HDLs can deliver sphingolipids to the surface of these cell types and activate sphingosine phosphate receptors. Sphingosine phosphate receptors are coupled to numerous different intracellular signaling cascades exerting roles in vasodilatation, inflammation, cell migration and apoptosis, inhibition of platelet activation, and endothelial adhesion molecule expression, among other functions. The ability of HDL to influence such a diverse array of cellular functions lends biological plausibility to the substantial epidemiological and clinical evidence suggesting that the HDLs are unique among lipoproteins in that they are vasculoprotective and antiatherogenic.