Fig. 1.

Putative contributions of HDL endocytosis and resecretion to RCT.

ApoA-I is secreted by the liver and intestine (not shown here) and acquires phospholipids and cholesterol. To exert athero-protective effects, apoA-I and HDL have to be transported to macrophage foam cells through endothelial cells. ABCA1 is necessary for apoA-I transcytosis through endothelial cells, whereas SR-BI, ABCG1 and ecto-F₁-ATPase facilitate HDL transport. Excess macrophage free cholesterol is transported to apoA-I by ABCA1 or to HDL by SR-BI. In addition, HDL retro-endocytosis was shown to mediate cholesterol efflux. ABCG1 mainly seems to have a role in intracellular cholesterol trafficking. Cholesterol enriched HDL then leaves the plaque via the lymphatics and the vasa vasorum and is transported back to the liver. Here, SR-BI transfers cholesterol to hepatocytes by selective lipid uptake. In addition, SR-BI, CD36 and a low affinity HDL binding site under the control of ecto-F₁-ATPase and P2Y13 are discussed to mediate HDL holo-particle uptake. After endocytosis, HDL is either rapidly recycled through the endosomal recycling compartment (ERC) and resecreted or transported to multivesicular bodies (MVBs). HDL degradation in lysosomes is limited and occurs rather slowly. During endocytosis, HDL exchanges cholesterol with hepatocytes. Cholesterol is then either used for the formation of new lipoproteins or secreted into the bile directly or indirectly after conversion to bile-acids.

Abbreviations: FC (free cholesterol); CE (esterified cholesterol); apoA-I (apolipoprotein A-I); HDL (high-density lipoprotein); SR-BI (scavenger receptor class B, type I); ABCA1 (ATP-binding cassette transporter A1); ABCG1 (ATP-binding cassette transporter G1); CD36 (cluster of differentiation 36).