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Sobenin et al. Desialylated LDL in diabetes

and was supposedly dependent on the proportion of desialylated LDL subfractions from type 2 diabetic
desialylated (atherogenic) LDL in total preparation and patients were much more effective than that from
of the extent of its desialylation. type 1 diabetic patients, with respect to intracellular
cholesterol accumulation.
The effects of sialylated and desialylated LDL
fractionated by density on intracellular cholesterol Size of sialylated and desialylated LDL
content was also studied. The results from the The size of total, sialylated, and desialylated LDL
experiment performed using LDL subfractions obtained particles was assessed according to their migration
from type 1 and type 2 diabetic patients are shown in distance in polyacrylamide gradient gel electrophoresis
Figure 2. The LDL samples from all patients produced performed under non-denaturing conditions. As shown
similar but quantitatively different effects. Sialylated in Table 3, in every studied group, desialylated LDL
LDL did not induce an increase in the intracellular particles appeared significantly smaller than the those
cholesterol content after 24 h of incubation under the in the total LDL preparation and more so than those
cell culture conditions. However, the densest sialylated in the sialylated LDL fraction. However, there was no
LDL subfractions (d > 1.042 g/mL) produced a moderate significant difference in LDL size between non-diabetic
but significant rise in intracellular cholesterol level. individuals, type 1, and type 2 diabetic patients,
Subfractions of less dense desialylated LDL (1.025- with respect to either total LDL, sialylated LDL, or
1.035 g/mL) also produced no significant atherogenic desialylated LDL.
effect, but LDL of greater density stimulated 1.3- to
2.3-fold cholesterol accumulation (P < 0.05). Denser Electrophoretic mobility of sialylated and
desialylated LDL
The surface net charge of sialylated and desialylated
LDL was judged according to their electrophoretic
mobility in agarose gel. As shown in Table 4,
desialylated LDL fractions in both non-diabetic and
diabetic patients had higher mobility than sialylated
LDL fractions, and this difference was statistically
significant among diabetic patients (P = 0.041).
Sialylated LDL from diabetic patients also seemed to
have higher mobility than sialylated LDL from normal
controls, but this difference was not statistically
L
significant [Table 4].

Table 2: The effect of total, sialylated and desialylated
LDL on intracellular cholesterol level
Cholesterol accumulation, % above control
Group
Total LDL Sialylated LDL Desialylated LDL
Healthy subjects 5 (3) 3 (3) 26 (9)* †‡
Type 1 diabetic 47 (10)* 9 (2) † 110 (45)* †‡
patients
Type 2 diabetic 100 (29)* 19 (10) † 169 (33)* †‡
patients
*Significant intracellular cholesterol accumulation, P < 0.05 vs.
‡
†
control; significant difference from total LDL, P < 0.05; significant
difference from sialylated LDL, P < 0.05. LDL: low-density lipoprotein
L
Table 3: The size of total, sialylated and desialylated
LDL particles
LDL particle size, nm
Group
Figure 2: Atherogenic effects of sialylated (hollow circles) and Total LDL Sialylated LDL Desialylated LDL
desialylated (filled circles) LDL density subfractions from type 1 (A) Healthy subjects 25.4 (1.2) 26.6 (1.4) 23.1 (0.9)* †
and type 2 (B) diabetic patients. Atherogenic effect was assessed Type 1 diabetic 26.6 (1.9) 27.2 (1.0) 22.5 (0.6)* †
as the ability of LDL (50 μg/mL) to induce significant increase in patients
the cholesterol content of subendothelial cells cultured from normal †
human aortic intima. Intracellular cholesterol content is expressed as Type 2 diabetic 25.1 (0.7) 26.3 (1.2) 22.3 (0.5)*
the percentage of cholesterol level in control cells. The rectangular patients
shaded areas denote the range of statistically insignificant changes in *Significant difference from total LDL, P < 0.05; significant difference
†
intracellular cholesterol level. LDL: low-density lipoprotein from sialylated LDL, P < 0.05. LDL: low-density lipoprotein
Vessel Plus ¦ Volume 1 ¦ March 31, 2017 33