Lipoprotein aggregation as an essential condition of intracellular lipid accumulation caused by modified low density lipoproteins

We have tested a hypothesis that aggregates of modified low density lipoproteins (LDL) play the key role in the accumulation of lipids by cells of unaffected aortic intima. It was demonstrated using analysis of relative dispersion of light transmission fluctuations as well as gel filtration on Sepharose CL-2B that LDL modified by oxidation, glycosylation, desialylation and malondialdehyde treatment form aggregates under the conditions of culture. Native LDL failed to aggregate under the same conditions. It was demonstrated that modified LDL, unlike native LDL, bring about a 2- to 3-fold rise in cholesteryl ester levels of cultured cells. Moreover, direct and strong correlation (r = 0.86) was observed between the degree of lipoprotein aggregation and the amount of cholesteryl esters accumulated. Removal of modified LDL aggregates by filtration through a 0.1 micron filter or gel filtration completely prevented the intracellular accumulation of cholesteryl esters. These findings indicate that LDL aggregates play an essential, if not the decisive, role in the intracellular accumulation of lipids in vitro.