All cells use and rely on fats and, for all animal cells, cholesterol as building blocks to create the multiple membranes which cells use to both control internal water content, internal water soluble elements and to organize their internal structure and protein enzymatic systems.
Lipoproteins in the blood, an aqueous medium, carry fats around the body. The protein particles have hydrophilic groups aimed outward so as to attract water molecules; this makes them soluble in the salt water based blood pool. Triglyceride-fats and cholesterol are carried internally, shielded from the water by the protein particle.
The interaction of the proteins forming the surface of the particles with (a) enzymes in the blood, (b) with each other and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.
Regarding atheroma development and progression vs. regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.
General categories of lipoproteins, listed in order from larger and less dense (more fat than protein) to smaller and denser (more protein, less fat):
|Density (g/mL)||Class||Diameter (nm)||% protein||% cholesterol||% phospholipid||% triacylglycerol|
In the bloodstream, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent chylomicron; the chylomicron is now considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes a hydrolysis reaction that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage.
The hydrolyzed chylomicrons are now considered chylomicron remnants. The chylomicron remnants continue circulating until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.
As in chylomicron metabolism, the apolipoprotein C-II and apolipoprotein E of VLDL particles are acquired from HDL particles. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature.
Again like chylomicrons, VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by preipheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase.
Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low density lipoproteins (LDL), which contain a relatively high cholesterol content. LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 or E on the LDL molecule. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.