OXIDATION OF LDL - ROLE IN ATHEROGENESIS

Oxidation of LDL is proposed to accelerate atherogenesis by the following sequence of events. LDL accumulates in atheroselerotic plaques, presumably due to interaction with intimal proteoglycans. The LDL then undergoes oxidation, and aldehydic products of lipid peroxidation such as HNE or other aldehyde products derived from lipid peroxidation, induce blocking of lysine residues on apo B. This results in its recognition by the scavenger receptor on tissue macrophages at sites in which LDL concentrations are low. At sites in which the LDL concentration is high, modification with such products induces intermolecular cross-linking and particle aggregation. The aggregated, oxidized LDL particles are then phagocytosed by tissue macrophages to induce lipid loading of these cells and the formation of foam cells, a characteristic of the earliest atherosclerotic lesion. By these mechanisms oxidation of LDL accelerates atherogenesis.