Reverse cholesterol transport

Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver via the plasma.

Cholesterol from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 (ATP-binding cassette transporter). ApoA-1 acts as an acceptor, and the phospholipid component of HDL acts as a sink for the mobilised cholesterol. The cholesterol is converted to cholesteryl esters by the enzyme LCAT (lecithin-cholesterol acyltransferase). The cholesteryl esters can be transferred to other lipoproteins (such as LDL), and these lipoproteins can be taken up by the liver through its LDL receptors.

However, the receptor SR-B1 (scavenger receptor class B1) present on the liver cells’ plasma membranes mediates most of the liver’s uptake of cholesteryl esters from HDL in the absence of uptake of apolipoproteins. The overall process by which HDL removes cholesterol from extrahepatic tissues and returns it to the liver is called reverse cholesterol transport. Once in the liver, the cholesteryl esters are converted to cholesterol and enter the general pool. Therefore, the liver can eliminate cholesterol from the body by secreting unesterified cholesterol into the bile or by converting cholesterol to bile acids.

Uptake of HDL2 is mediated by hepatic lipase, a special form of lipoprotein lipase found only in the liver. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of HDL2 in women.