Loss of apolipoprotein E synthesis causes increased serum cholesterol concentrations and the sensitivity to high-fat diet in mice. We analyzed the changes in lipoprotein and hepatic structures in apolipoprotein E-deficient mice kept on control diet and cholesterol diets. Basal cholesterolemia of heterozygous (+/-) mice (2.2±0.28 mmol/l) was the same compared to wild-type (+/+) mice (2.3±0.15 mmol/l), but was lower compared to homozygous (-/-) mice (10.3±1.40 mmol/l). In +/- mice, cholesterolemia rose to 3.2 mmol/l on cholesterol diet and to 9 mmol/l on cholate diet, to 3 mmol/l and 3.6 mmol/l in +/+ mice, and to 23.4 mmol/l and 70.5 mmol/l in -/- mice, respectively. While the ratio of cholesterol/triglyceride concentrations in VLDL, IDL and LDL fractions was not increased in +/- mice and +/+ mice, it was increased in -/- mice on control diet. On the cholesterol diet, this ratio rose and was dramatically increased by cholate diet in all groups of mice. Even though cholate supplementation increased cholesterol concentration, it led to substantial toxic changes in hepatic morphology of all animals. In conclusion, one functional apo E allele in +/- mice is effective in keeping serum cholesterol concentrations in normal range on a control diet, but not on the cholesterol and cholate diets.
Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol > 4.1 mmol/l or triglycerides > 2.5 mmol/l or taking any of lipid lowering drugs) – 94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals – 30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13±3.07 vs. 5.41±3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68±0.22 vs. 0.58±0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77±9.54 vs. 56.49±7.80 U/l; p=0.015), malondialdehyde (0.89±0.09 vs. 0.73±0.08 µmol/l; p=0.010) and nitrites/nitrates (20.42±4.88 vs. 16.37±4.44 µmol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.