Reverse Cholesterol Transport

Cholesterol synthesised outside the liver needs to brought back to the hepatocytes. The main purpose of this process is the removal of access cholesterol from organs and tissues to the liver so that it can be secreted as bile. The transport of cholesterol from the peripheral tissues back to the liver is known as Reverse cholesterol transport (RCT).

Access cholesterol if allowed to accumulate at a site could increase monocyte recruitment and increased inflammatory responses. The process of RCT is of particular importance in arteries as it prevents accumulation of access cholesterol and prevents atherogenesis. This then leads to the process of increased foam cell formation and formation of atherosclerotic plaques.

A critical step in RCT is the efflux of cholesterol from inside of macrophages or foam cells to the outside using a transporter called ATP-binding membrane cassette transporter A1 (ABCA1). The cholesterol transported out of the cell binds to apolipoprotein E in the plasma that takes it to the liver.

It is seen that individuals with the mutated version of the ABCA1 gene is at high risk of atherosclerosis. A mutation in ABCA1 leads to a condition called Tangier disease where the individual suffers from the absence of high density protein (HDL – good cholesterol) and increased levels of low density lipoprotein (LDL – bad cholesterol). This results in the reduced removal of access cholesterol from the cells leading to the formation of foam cells. The phenomenon of reduced HDL levels in the blood is termed as hypercholesterolemia. This results in the accumulation of access fat in the body and often nerve dysfunction.