Figure 1.

Schematic representation of HDL multi-protective mechanisms. The principal function of HDL is the reverse cholesterol transport (RCT). In atherosclerotic lesions, HDL induces cholesterol efflux from macrophages, avoiding foam cells formation. The process starts with premature HDL (Nascent HDL) that interacts with ATP-binding cassette transporter A1 (ABCA1), expressed on macrophages, and acquires phospholipids and free cholesterol. This nascent HDL evolves in mature HDL (HDL3) that further acquires cholesterol, cholesterol ester, and triglycerides via specific enzymes and interacting with other lipid transporters such as scavenger receptor class B type I (SR-BI) and ATP Binding Cassette Subfamily G Member 1 (ABCG1). This large HDL (HDL2) turns to the liver and after binding SR-BI, cholesterol esters are internalized and degraded and excreted into the bile. The second mechanism for cholesterol degradation is mediated by mature low-density lipoproteins (LDLs) that uptake cholesterol from HDL2 mediating cholesterol internalization by hepatocytes via the LDL receptor (LDL-R). Other important functions of HDL include anti-thrombotic activities (increased expression of nitric oxide [NO] and prostacyclin [PG12] in endothelial cells with reduced platelet activation and augmented fibrinolysis), anti-inflammatory effects (reduced monocytes activation), immunomodulatory properties (lymphocytes anergy), and anti-oxidant effects (prevention of LDL oxidation).