High density lipoprotein physiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayokunle Olubaniyi, M.B,B.S [2]

Overview

As mentioned above, the HDL is synthesized in liver and intestines as small nascent particles, composed mainly of phospholipids and apolipoproteins.
As it travels in the blood it acquires surface components, like more phospholipids, cholesterol and apolipoproteins, from triglyceride depleted chylomicrons and remnants of VLDL.
As this initial HDL particle contains less amounts of cholesterol, it acquires free unesterified cholesterol from tissues of the liver and arterial walls. This hydrophobic free cholesterol sinks into the center of the HDL particle. The Apolipoprotein A1 acts as a signal protein in mobilizing cholesterol esters from within the cells.
In the peripheral tissues, the nascent HDL particles interact with a cell surface protein called ABCA1 (also known as cholesterol efflux regulatory protein, CERP). High cholesterol levels induce expression of ABCA1 gene and production of the protein. Mutations of this transport protein gene causes familial HDL deficiencies and Tangier disease. The HDL also accepts cholesterol from triglycerides that has undergone lipolysis.
Once the cholesterol is acquired by the nascent HDL particles from the peripheral tissues, it gets esterified by a plasma enzyme LCAT (Lecithin-cholesterol acyltransferase). This enzyme is activated by apolipoprotein A1 .