Figure 10. Beneficial Functions of HDL. HDL mediates a number of atheroprotective processes. HDL is critical in reverse cholesterol transport where it mediates the first step of removing cholesterol from the periphery and macrophage foam cells for clearance by the liver. HDL can directly mediate the last step in reverse cholesterol transport by delivering cholesterol to the liver via interaction with SR-BI. HDL reduces LDL oxidation and cell oxidative status by removing lipid hydroperoxides from LDL and cells. HDL also prevents LDL oxidation via its anti-oxidant enzymes (PON1, LCAT, and Lp-PLA2) and by the reduction of lipid hydroperoxides by apoA-I. HDL maintains the endothelial cell barrier by stimulating vasorelaxation resulting from enhanced nitric oxide production from HDL induced signaling via a number of endothelial cell receptors (SR-BI, S1P, ABCG1). HDL prevents thrombus formation by inhibiting coagulation factors and by stimulating efflux of cholesterol from platelets via SR-BI to reduce platelet aggregation. HDL prevents endothelial cell and macrophage apoptosis by signaling pathways which modulate expression of the pro-apoptotic protein, Bid, and the anti-apoptotic factor, Bcl-xl. HDL also reduces apoptosis susceptibility by alleviating endoplasmic reticulum stress by removing excess free cholesterol and lipid hydroperoxides from cells. HDL limits atherosclerotic lesion inflammation by inhibiting endothelial cell activation resulting in less monocyte recruitment. HDL also reduces lesion inflammation by promoting the macrophage anti-inflammatory M2 phenotype via ABCA1/ JAK2 signaling to enhance anti-inflammatory cytokine production (IL-10, TGF-β). HDL inhibits conversion to the macrophage inflammatory M1 phenotype by preventing antigen-specific activation of T helper 1 (Th-1) cell to produce interferon gamma. HDL contains an array of proteins and bioactive lipids that regulate HDL function. In addition, HDL controls a number of atheroprotective processes by modulating gene expression by transferring microRNAs to recipient cells.