High-density lipoproteins apoE-containing

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Normal serum was recently demonstrated to contain substances inhibiting permeability factor(s). These inhibitors are not present in sera of patients with FSGS (Sll). Some of these inhibitors have been identified as apolipoproteins of the high-density lipoprotein (HDL) complex, for example, apo J, apo E2, and apo E4 (C2). Inhibitors of the permeability factors may be lost in urine in patients with nephrotic syndrome and their presence in urine has been documented (G5). FSGS may thus be caused not only by the (increased) production of permeability factors, but also by the urinary loss of their inhibitors. Bioassay (S5) is not able to differentiate between increased production of permeability factors and the loss of their inhibitors. Increased permeability was confirmed by this bioassay even in patients with FSGS and the documented mutation of the podocin gene, apparently without increased production of the permeability factors (G5). 

Aldehyde-protein adducts and hydroxyl radicals also stimulate immunological responses directed against the specific modifications of proteins. High antibody titres have been observed from patients with severe alcoholic liver disease, particularly IgA and IgG autoantibodies. Such antibodies have considerable specificity towards aldehyde-lysine residues. Alcohol consumption markedly increases the hepatic output of very low-density lipoprotein (VLDL), but decreases the low-density lipoprotein (LDL) levels and apolipoprotein B. Ethylation of apo-B-lysine renders LDL immunogenic and accelerates its clearance. Alcoholics have been shown to develop acetaldehyde adducts in apo-B-containing lipoproteins, particularly VLDL. 

In addition, in species with high concentrations of HDL-with apoE, it has been postulated that this lipoprotein class serves to transport excess cholesterol from peripheral cells to the liver for elimination from the body (Mahley et al, 1980). This transport process is referred to as the reverse cholesterol transport process (Glomset, 1968). In contrast, in species with high CETP activity, the excess cholesterol from the periphery is transferred from the typical non-apoE-containing HDL to the lower density lipoprotein classes (VLDL, IDL, and LDL) for clearance by the liver. 

The type of lipoprotein assembled and secreted by the liver is very low-density lipoprotein (VLDL). It contains a high ratio of triglyceride to cholesterol. The main apoprotein in VLDL is apo-Bl 00 which is derived from the same gene as the chylomicron-specific apo-B48. The latter apoprotein is slightly shorter because the mRNA in the intestinal cells is posttranscriptionally altered to introduce a premature stop codon. 

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