Blood - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 12

High-density lipoproteins are circulating stores of cholesterol, cholesteryl esters,
and apolipoproteins (ApoA1, -A2, -A4, -C1 to -C4, -D to -F, -H, -J, -L1, and -M) 21
delivered to the liver, where they are endocytosed. Molecule HDL-cholesterol may
be esterified in the plasma by lecithin-cholesterol acyltransferase (LCAT). Free
and esterified cholesterols are removed from HDL in the liver using scavenger
receptor ScaRb1, and afterward excreted into the bile. Several proteins, such
as lecithin-cholesterol acyltransferase, paraoxonase Pon1, and platelet-activating
factor acetylhydrolase (PAFAH), 22 are associated with HDL particles.
High-density lipoproteins contain [ 13 ]: (1) numerous proteins, such as enzymes
and apolipoproteins, as well as (2) various lipids, not only free and esterified choles-
terol, but also phospholipids (phosphatidylcholine, phosphatidylethanolamine, plas-
malogen, lysophosphatidylcholine, glycerophospholipids), free and esterified fatty
acids (mono- and triacylglycerols), and sphingolipids (ceramide, sphingomyelin,
sphingosine 1-phosphate, lysosulfatide, and sphingosylphosphorylcholine).
Several HDL types differ in density, shape, size, and surface charge. Therefore,
HDLs are heterogeneous in structure, physicochemical properties, metabolism, and
activity. Small, lipid-poor, nascent HDLs are made of apolipoproteins embedded in
a lipid monolayer of phospholipids and free cholesterol. They are mainly produced
by the liver and intestine or can be released as fragments from triglyceride-
rich lipoproteins. Large, mature HDLs contain a core of cholesteryl esters and
triglycerides.
Nascent HDLs acquire cholesterol and phospholipids at cell membranes upon
efflux via ATP-binding cassette transporter-A1. Esterification of HDL cholesterol
from pre

-HDLs by lecithin cholesterol acyltransferase generates: (1) small, dense,
cholesterol-poor HDL3 and (2) large, light, cholesterol-rich HDL2 that, in turn, can
be converted to HDL3 (Fig. 1.2 ).
Metabolism of HDLs involves several processes, such as exchange of cholesteryl
esters and triglycerides between HDLs and apoB-containing lipoproteins, uptake of
cholesteryl esters by hepatocytes via scavenger receptor-B1, and phospholipid and
triglyceride hydrolysis by hepatic lipase. Cholesterol acquired by HDLs can also be
transferred to VLDLs and LDLs by cholesterol ester transfer protein (CETP). 23

β

21 ApoA1, ApoA2, ApoA4, ApoB, ApoC3, ApoD, ApoE, ApoH, LCAT, and CETP are detected in
the ApoA4-containing lipoproteins [ 12 ].
22 A.k.a. serine-dependent phospholipase-A2 (Vol. 4 - Chap. 2. Signaling Lipids).
23 The glycoprotein cholesteryl ester transfer protein (CETP) acts in cholesterol distribution
among plasma lipoproteins. CETP transfers not only cholesteryl esters, but also triglycerides
and phospholipids between lipoproteins, including VLDLs, LDLs, HDLs, and chylomicrons.
“Bad” cholesterol is mainly found in low-density lipoproteins, “good” cholesterol in high-density
lipoproteins. Protein CETP mediates the transfer of cholesteryl esters from HDL to ApoB-
containing lipoproteins in exchange for triglycerides. Agent ApoC1 abolishes CETP activity [ 14 ].
Lipid transfer inhibitor protein (LTIP or ApoF) regulates CETP activity in LDLs.