Modified lipoproteins in atherosclerosis and diabetes

Abstract

In atherosclerosis and diabetes functional and structural changes of lipoproteins occur as a result of peroxidation and glycation. LDL is the most modified fraction among the lipoproteins. Oxidation of LDL which probably occurs in subendotelial space is associated with the lipid peroxidation of PUFAs forming lipid hydroperoxides and fragmentation of apoB. As a result oxidized LDL has a different characteristic in electrophoresis and has less PUFA more aldehydes, more lysophosphatidylcholine in the lipid phase and degraded apoB. The alterations lead to some functional changes in LDL. Oxidation causes some cytotoxic effects in the cells. Increased monocyte binding, inhibition of endothelial derived factor (EDRF), increased expression of endotelin mRNA, induction of PGI2 synthesis from endothelial cells are some of the oxidized LDL related changes of the cells. Antibodies against oxidized LDL are also found in atherosclerotic patients and suggest that it is important in the atherogenic effect of LDL. Glycation is another change in the structure of LDL in diabetes resulting from the increased glucose concentration. In vivo glycation is linked with oxidation. Autoxidation of glucose and Amadori rearrangement products causing lipid peroxidation and forming superoxide radicals or decreased clearance of glycated proteins are the possible mechanisms.