Summary
Highlights
Apolipoproteins are crucial for effective treatment of cardiovascular disease by orchestrating the transport of lipids throughout the body, including triglycerides for energy/storage and cholesterol for cell membrane/hormone synthesis. This system also includes reverse cholesterol transport.
Apo-containing lipoproteins (non-HDL) manage lipid delivery, while Apo A1-containing lipoproteins (HDL) handle reverse cholesterol transport. These particles, originating from intestinal ApoB48 and hepatic ApoB100 lineages, are continuously remodeled, releasing triglycerides and becoming cholesterol-rich remnants.
Newly assembled apo-containing lipoproteins are secreted, acquiring ApoE, C2, and C3. ApoC2 activates lipoprotein lipase (LPL), hydrolyzing triglycerides into fatty acids for peripheral tissue. These lipoproteins become smaller remnants, with hepatic lipase transforming ApoB100 remnants into LDL. Most Apo remnants are recycled to the liver, but LDL can be taken up by peripheral cells or deposited in arterial walls, leading to atheroma.
The Apo A1 or HDL pathway protects against atherogenesis through reverse cholesterol transport and by preventing LDL oxidation. Poorly lipiated Apo A1 is secreted and circulates, removing excess cholesterol from peripheral cells, especially cholesterol-laden arterial wall macrophages, forming nascent HDL.
Excess cholesterol in macrophages triggers ABCA1 transporter upregulation, converting cholesterol esters to free cholesterol, which ABCA1 then delivers to poorly lipiated Apo A1 to form nascent HDL. Free cholesterol on HDL is esterified by LCAT, forming mature HDL3. HDL3 removes more cholesterol via SRB1 receptors, expanding to HDL2 as it collects more cholesterol.
Cholesterol-rich HDL2 exchanges cholesterol ester for triglycerides from apo-containing lipoproteins via CETP, further enriching apo-lipoproteins with cholesterol and HDL with triglycerides. HDL can then be hydrolyzed by hepatic lipase (returning to HDL3), interact with SRB1 in the liver (returning to HDL3), or be catabolized by the liver.
The complementary lipoprotein systems work in harmony to manage the body's lipid needs. Continued scientific understanding of these intricate normal lipid metabolisms improves our ability to diagnose and manage various dyslipidemias.