Kanna Sasai

Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography

We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms and the finding in coronary angiography. Four CETP-deficiency heterozygotes were identified and excluded from the analysis. CETP mass level showed neither significant correlation with the coronary score (CS) (r=0.06, P=0.52) nor the difference between the groups eventually diagnosed as coronary heart disease (CHD) positive and CHD negative (2.36+/-0.57 vs. 2.24+/-0.21, P=0.24). CETP mass correlated with the total and LDL cholesterol (r=0.43, P<0.001; r=0.36, P<0.001, respectively) but not with HDL cholesterol (r=0.08, P=0.40). While I405V polymorphism had no impact on CETP mass, HDL cholesterol or CS, CETP mass was low with TaqIB polymorphism (B1B1>B2B2, P<0.05) only in the low CS group (<4). Among the lipid and lipoprotein, HDL cholesterol had a greater impact than LDL cholesterol on coronary atherosclerosis. We concluded that CETP mass in plasma does not correlate with coronary atherosclerosis as whole in the non-CETP-deficient. However, the B2B2 genotype in CETP TaqIB polymorphism, only when it decreases the CETP level, may act as a protective factor against atherosclerosis. It should also be noted that CETP mass in general correlates to total and LDL cholesterol, so that it would be an indirect atherogenic parameter.

Effects of vitamin C and vitamin E on plasma levels of lipid hydroperoxides and thiobarbituric acid reactive substance in humans

Abstract A study was conducted to investigate the effects of vitamin C and vitamin E on plasma levels of lipid hydroperoxides (LPO) and thio-barbituric acid reactive substance (TBARS) in human volunteers to identify the step in the lipid peroxidation cascade at which these vitamins act. Forty subjects (20 men and 20 women) were randomly assigned to receive either vitamin C or vitamin E. Twenty subjects received 500 mg of vitamin C daily for 4 weeks, and 20 subjects received 300 mg of vitamin E daily for 4 weeks. Blood samples were collected before and 4 weeks after vitamin treatment, in the morning, after the subjects had fasted for 12 hours. Plasma levels of LPO and TBARS were determined. Plasma levels of lipids, apolipoproteins, vitamin C, and vitamin E were also measured. Vitamin C significantly reduced plasma levels of LPO and TBARS. Vitamin E significantly increased plasma levels of LPO and significantly reduced plasma levels of TBARS. Plasma concentrations of vitamin C and vitamin E significantly increased after 4 weeks of vitamin treatment. There were no significant changes in the plasma levels of lipids except LPO, TBARS, and apolipoproteins. From these results, it was concluded that vitamin C reduced LPO and TBARS levels, and vitamin E increased LPO levels and reduced TBARS levels.

Plasma concentrations of LPL and LCAT are in putative association with females and alcohol use which are independent negative risk factors for coronary atherosclerosis among Japanese.

BACKGROUND Coronary heart disease (CHD) prevalence appears low among Japanese. Analysis of their negative risk factors is therefore important for public health strategy. METHODS We analyzed the impact on coronary atherosclerosis of sex, alcohol intake, plasma lipoproteins and enzymes to regulate cholesterol transport, lipoprotein lipase (LPL) and lecithin:cholesterol acyltransferase (LCAT) for the 110 patients who underwent coronary angiography, consecutively enrolled by excluding those >70 years or under hypolipidemic-drug treatment. Subgroup combinations compared were males vs. females in non-drinkers, and drinkers vs. non-drinkers in males. RESULTS Coronary stenosis was less in females and in drinkers, accompanied by high-density lipoprotein (HDL) in the respective comparison. LPL associated with sex (females>males) and LCAT with alcohol intake (drinkers>non-drinkers) although neither enzyme demonstrated direct correlation with coronary stenosis. LPL positively associated only with HDL in most of subgroups and LCAT correlated with low-density lipoprotein (LDL) in all subgroups but with HDL only in males. CONCLUSIONS Among non-drinkers, females are at lower risk for coronary atherosclerosis than males mainly due to higher HDL in potential association with high LPL, and that drinkers are protected among males also by high HDL that is in apparent association with LCAT.

Strong synergistic anti-peroxidative effects of HDL3 and ascorbic acid against copper-catalyzed LDL peroxidation

The aim of this study was to investigate the effects of high density lipoprotein 3 (HDL3) and ascorbic acid (AsA) in combination on copper-catalyzed low density lipoprotein (LDL) peroxidation. LDL and HDL3 were isolated from sera of healthy volunteers. LDL protein, 200 microg/ml, was incubated in phosphate-buffered saline (PBS) containing 2.5 microM CuSO4 in the absence or presence of AsA, with HDL3 protein alone, or with coincubation of HDL3, 200 microg/ml, and AsA, 20 microg/ml, at 37 degrees C for up to 24 h. As a control, the same amount of control LDL protein was added to PBS. The protective effects of the HDL3 and AsA were examined by both electrophoresis and determination of the lipid hydroperoxide (LPO) level in each sample. The concentration of AsA was also measured in samples containing AsA. The coincubation of HDL3 and AsA exerts more powerful anti-peroxidative effects against copper-catalyzed LDL peroxidation, than either of these agents alone. In addition, AsA was retained in the media by the addition of HDL3. The findings suggest that there are strong synergistic anti-peroxidative effects of HDL3 and AsA and these two may act in concert in vivo to inhibit LDL peroxidation and thus exert an anti-atherosclerotic effect.