Fructose ingestion enhances atherosclerosis and deposition of advanced glycated end-products in cholesterol-fed rabbits.

This study was performed to investigate whether the plasma concentration of phosphatidylcholine hydroperoxide (PCOOH), which is a marker of oxidized stress in the blood, increased in cholesterol-fed rabbits, and fructose ingestion promoted this process and aggravated atherosclerosis. Male Japanese white rabbits (age: 12 weeks, and body weight: around 2.0 kg, n = 15) were divided into three groups, (1) a NN group as a normal control fed a standard diet (n = 5), (2) a CN group fed 1.0% cholesterol, and (3) a CF group given both 1.0% cholesterol and 10% fructose-containing tap water. During 8 weeks, plasma PCOOH levels increased significantly in the CN and CF groups compared to the NN group and fructose further raised the PCOOH level. The atherosclerosis was significantly promoted and the deposition of advanced glycation end products (AGEs) was marked in the CF group compared to the CN group. Fructose worsened the atheromatous lesions caused by cholesterol feeding. The mechanism is most likely through lipid peroxidation, which was increased by cholesterol feeding-induced hyperlipidemia, and the formation of AGEs.

Telomere shortening of peripheral blood mononuclear cells in coronary disease patients with metabolic disorders.

OBJECTIVE: Telomere shortening is correlated with cell turnover and aging, but it has been recently suggested to occur not only by aging but by several biochemical factors of metabolic disorders predisposing to atherosclerosis. PATIENTS AND METHODS: We compared telomere length of peripheral blood mononuclear cells of patients with the metabolic disorders, hypercholesterolemia (HC) and diabetes mellitus (DM), according to the presence or absence of coronary diseases. RESULTS: The results demonstrated that HC and/or DM patients with coronary diseases have significantly shorter telomere length than healthy controls (p = 0.0014). CONCLUSION: Telomere shortening may be involved in the mechanisms that promote coronary diseases under some circumstances of metabolic disorders.

Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: comparison among CETP/TaqIB genotype subgroups.

We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments.

Increase of serum phosphatidylcholine hydroperoxide dependent on glycemic control in type 2 diabetic patients.

In order to clarify the relationship between serum phosphatidylcholine hydroperoxide (PCOOH) levels and blood glucose control in type 2 diabetes patients (DM), DM (n = 61) and normal control (n = 11) were enrolled. High-density lipoprotein (HDL) was separated from serum by the addition of sodium phosphotungstate and magnesium chloride, and the precipitated fraction was prepared as non-HDL. Phospholipids were extracted from whole serum, non-HDL and HDL to estimate PCOOH level with chemiluminescence high performance liquid chromatography (CL-HPLC). PCOOH level (nmol/l, mean +/- S.D.) was higher in DM than in control (33.1 +/- 9.5 vs. 23.0 +/- 8.2 for serum; P < 0.01, 17.0 +/- 5.5 vs. 10.6 +/- 3.8 for non-HDL; P < 0.01, and 16.1 +/- 6.3 vs. 12.3 +/- 5.5 for HDL; not significant, respectively). DM was divided into five groups according to hemoglobin A(1c) (HbA(1c)) levels (%): (1) less than 6, (2) 6-6.4, (3) 6.5-6.9 (4) 7.0-7.4, and (5) over than 7.5. Increase of PCOOH levels was dependent on HbA(1c). We concluded that (1) serum and non-HDL PCOOH increased in DM, (2) the level was strongly correlated with diabetic control, and (3) approximately a half amount of serum PCOOH was present in HDL of both control and DM.