VLDL are assembled in the liver, and contain newly synthesized triacylglycerol, cholesterol and cholesteryl esters and phospholipids as well as lipids from chylomicron remnants. These lipids are taken up by peripheral tissues which have cell-surface lipoprotein lipase, phospholipase and cholesterol esterase.
As the VLDL particles are progressively depleted of lipids, they transfer apoproteins C-I and C-II to HDL, forming intermediate-density lipoprotein particles (IDL). IDL take up cholesteryl esters from HDL, becoming LDL.
LDL are cleared from the circulation by receptor-mediated uptake in the liver. Both the receptor and the LDL are internalized; the LDL is hydrolysed in lysosomes by proteases and lipases, and the receptor is recycled back to the cell surface.
Cholesterol represses synthesis of the LDL receptor, so that when there is an adequate amount of cholesterol in the liver less LDL will be cleared. The hypocholesterolaemic statin drugs both inhibit cholesterol synthesis and also increase clearance of LDL, because there is now less repression of receptor synthesis.
As discussed in section 7.2, elevated LDL cholesterol is one of the major factors in the development of atherosclerosis and ischaemic heart disease. Two factors are involved in elevated LDL cholesterol:
LDL that are not cleared by the liver are taken up by the macrophage scavenger receptor; unlike hepatic uptake, this is an unregulated process, and macrophages can take up an almost unlimited amount of lipid from LDL. Lipid-engorged macrophages (foam cells) infiltrate blood vessel endothelium, forming fatty streaks that eventually develop into atherosclerotic plaque.
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