Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography

A part of low density lipoproteins (LDL) isolated from the blood of healthy subjects and patients with coronary atherosclerosis bind to a Sepharose-linked Ricinus communis agglutinin, a lectin that interacts specifically with galactose residues. Bound LDL can be replaced by galactose, but not other saccharide constituents of the LDL molecule (mannose, glucose, N-acetylglucosamine, sialic acid). Bound LDL subfraction has a 2-3-fold lower content of sialic acid as compared with unbound LDL. The blood content of desialylated LDL in atherosclerotic patients was about 3-fold higher (1.5- to 6-fold) than in healthy subjects. Desialylated LDL induced a 2- to 4-fold more intensive accumulation of total cholesterol in cultured human aortic intimal cells. Unbound LDL had no effect on intracellular deposition of lipids. It is suggested that the subfraction of desialylated LDL may be responsible for the atherogenicity of LDL isolated from blood of atherosclerotic patients.     

Combined effects of desialylated and glycosylated low density lipoproteins on lipid content of human aortic intima cells in vitro]

We have studied a combined effect of glycosylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycosylated LDL taken in the concentration of 50 and 100 mg/ml increased the cell cholesterol content by 30 and 70 percent, respectively. The effect of the same concentrations of glycosylated LDL treated with neuraminidase (desialylated-glycosylated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 mg/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycosylated (50 mg/ml) and desialylated (50 mg/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergic effects of desialylated and glycosylated lipoproteins as well as LDL with both types of modification.