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Zinc can either increase or decrease LDL oxidation
Monday 10 October 1994: Poster Abstracts Modified lipoproreins
Age (years, mean) Male (%) Previous MI (%) Diabetes (%) Smokers (%) TC (mgldl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Fibrinogen (mean)
Stroke (n = 45)
Others (n = 3078)
P<
61 k 6 41 (91) 37 (82) 9 (20) 10 (22) 209 f 17 145 + 16 34f5 151* 57 392 f 84
6Ok7 2817 (92) 2370 (77) 294 (10) 344 (10) 212f 18 148 + 17 35 + 6 149 * 52 349 f 73
NS NS NS 0.02 0.02 NS NS NS NS 0.0001
After multiple logistic regression analysis including all the above parameters, diabetes (RR = 2.14; 95% CI 1.00-4.55), smoking (RR = 2.10; 1.00-4.41) and an increase of 80 mg/dl in fibrinogen level (RR = 1.61; 1.22-2.14) emerged as independent predictors of stroke. Routine fibrinogen measurement should be considered in patients with CIHD. The effects of academic stress on lipid and lipoprotein levels in university students Kwon BK, m, Div. of Endocrinol., Queen’s Univ., Kingston, Cunada, K7L 2V7
1
The objective of this study was to examine effects of academic stress on plasma lipid and lipoprotein levels, and the influence of lifestyle factors (diet, sleeping habits, and physical activity) on observed lipid changes. 62 university students (28 males, 34 fe-
37
males) were studied 3 months before and again during final examinations. Psychological testing with the Multiple Affect Adjective Checklist revealed significant increases in raw scores for anxiety, depression and hostility (P < 0.001) during exams, indicating psychological stress. Mean TC, LDL-C and apo B levels during examinations were significantly higher than before (TC, 4.62 + 0.73 vs 4.33 f 0.75 mmol/l, P < 0.001; LDL-C, 2.86 f 0.66 vs 2.49 + 0.65 mmoUl, P < 0.001; apo B, 1.01 f 0.25 vs 0.89 zt lower 0.23 g/l, P < 0.001). HDL-C levels were significantly (1.22 k 0.25 vs 1.32 * 0.26 mmoV1, P < 0.001). Tg levels did not change (1.15 f 0.52 vs 1.12 * 0.48 mmolil, P = 0.475). Similar changes were observed for males and females. Lp(a) levels did not change significantly for the entire group. Only 14 students had baseline Lp(a) levels above 5.0 mg/dl (lower limit of detectability of the assay) and in this subset, the mean Lp(a) level increased significantly (22.7 vs 17.0 mg/dl, 33.5% increase, P < 0.022). Students exercised less during examinations (2.1 + 3.0 vs 4.4+ 5.1 h/week, P
MODIFIED LIPOPROTEINS
1138j Effects of water-soluble
plasma antioxidants on LDL oxidation USE, Leake DS, Dept. of Biochem. and Physiol., Univ. of Reading, Berkshire, RG6 2AJ, UK
It is generally believed that large-scale LDL oxidation does not occur within the circulation because of the antioxidant capacity of plasma. We have investigated the effects of various water-soluble plasma antioxidants on LDL oxidation. Human LDL (lOOpug protein /ml) was incubated with mouse resident peritoneal macrophages for 18 h at 37°C in Ham’s F-10 medium containing 6,uM iron and various concentrations of the antioxidant under study. The degradation and uptake of the LDL by 3774 macrophages was then measured. Macrophage-oxidized LDL was taken up by 5774 macrophages 3-10 times faster than control LDL. Lipoprotein-deficient fetal calf serum (5%) almost totally inhibited the oxidation of LDL. 50% inhibition of LDL oxidation was achieved with 4 g albumin/i, 2pM bilirubin, 0.75 PM apo-transferrin and 45-60pM ascorbate. 50 g albumin/l, 7.5 PM bilirubin, 3 PM apo-transfenin and 60-1OOpM ascorbate resulted in total, or near total, inhibition. The average plasma concentrations of these antioxidants are 40 g/l, 8.5pM, 30,~M and 20-55pM respectively. Holotransferrin. which is saturated with iron, was unable to inhibit LDL oxidation by macrophages, indicating that apo-transferrin must inhibit LDL oxidation by binding the iron ions in the medium that are essential for the modification of the LDL. These results support the belief that large-scale LDL oxidation is unlikely to occur within the circulation. 11391 Zinc can either increase or decrease LDL oxidation . m Leake DS, Dept. of Biochem. and Physiol., Univ. of Reading, Be&hire, RG6 ZAJ. UK We have investigated
the effect of zinc ions on iron-dependent
oxidation of LDL in vitro, because of its potential effects on atherosclerosis. Atherosclerotic lesions may well be acidic and so we have used buffers of various pHs. Human LDL was incubated for 18 h at 37°C in Ham’s F-10 medium (pH 7.4) or modified Hanks’ balanced salt solution (HBSS) at pH 7.4, 6.5 or 5.5 in the presence of 6yM Fe2” and cysteine (5OOyM in Ham’s F-10 or 1OOpM in HBSS). LDL oxidation was assayed by measuring hydroperoxides, thiobarbituric acid reactive-substances and uptake by 5774 macrophages. Zinc caused a dose-dependent inhibition of LDL oxidation in Ham’s F-10, with a half-maximal inhibition at l-3 PM. (In other experiments, Zn*+ also inhibited LDL oxidation by macrophages or endothelial cells in Ham’s F-10 medium.) LDL oxidation in HBSS increased with decreasing pH. At each pH, Zn2+ (up to increase in LDL oxida1OpM) caused a large dose-dependent tion. In Ham’s F-10, the antioxidant effect of zinc may possibly be explained by the displacement of iron from its binding sites on LDL, hence reducing the local oxidative stress. In HBSS, a much simpler buffer system, Zn2+ may increase LDL oxidation possibly by displacing iron from the phosphate ions making the iron more available. These results may help to explain why it is very unclear whether zinc is pro- or anti- atherogenic in vivo.
1
High density lipoproteins have antioxidative activity in vivo
WAN,
Gurevich VS, Nikiforova AA, Denisenko AD, Kuznetsov AS, Shatilina LV, Plavinsky SL, Dept. qf Biochem., Inst. of Exp. Med., 12 Acad. Pavlov Str., St. Petersburg 197376, Russia
It is known that addition of HDL to a solution of LDL slows down the formation of lipid peroxide products, both spontaneous and induced by iron and copper ions, xanthine-xantbine oxidase or endothelial cells. The question arises whether HDLs exert a
Atherosclerosis X, Montreal, October I994
Age (years, mean) Male (%) Previous MI (%) Diabetes (%) Smokers (%) TC (mgldl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Fibrinogen (mean)
Stroke (n = 45)
Others (n = 3078)
P<
61 k 6 41 (91) 37 (82) 9 (20) 10 (22) 209 f 17 145 + 16 34f5 151* 57 392 f 84
6Ok7 2817 (92) 2370 (77) 294 (10) 344 (10) 212f 18 148 + 17 35 + 6 149 * 52 349 f 73
NS NS NS 0.02 0.02 NS NS NS NS 0.0001
After multiple logistic regression analysis including all the above parameters, diabetes (RR = 2.14; 95% CI 1.00-4.55), smoking (RR = 2.10; 1.00-4.41) and an increase of 80 mg/dl in fibrinogen level (RR = 1.61; 1.22-2.14) emerged as independent predictors of stroke. Routine fibrinogen measurement should be considered in patients with CIHD. The effects of academic stress on lipid and lipoprotein levels in university students Kwon BK, m, Div. of Endocrinol., Queen’s Univ., Kingston, Cunada, K7L 2V7
1
The objective of this study was to examine effects of academic stress on plasma lipid and lipoprotein levels, and the influence of lifestyle factors (diet, sleeping habits, and physical activity) on observed lipid changes. 62 university students (28 males, 34 fe-
37
males) were studied 3 months before and again during final examinations. Psychological testing with the Multiple Affect Adjective Checklist revealed significant increases in raw scores for anxiety, depression and hostility (P < 0.001) during exams, indicating psychological stress. Mean TC, LDL-C and apo B levels during examinations were significantly higher than before (TC, 4.62 + 0.73 vs 4.33 f 0.75 mmol/l, P < 0.001; LDL-C, 2.86 f 0.66 vs 2.49 + 0.65 mmoUl, P < 0.001; apo B, 1.01 f 0.25 vs 0.89 zt lower 0.23 g/l, P < 0.001). HDL-C levels were significantly (1.22 k 0.25 vs 1.32 * 0.26 mmoV1, P < 0.001). Tg levels did not change (1.15 f 0.52 vs 1.12 * 0.48 mmolil, P = 0.475). Similar changes were observed for males and females. Lp(a) levels did not change significantly for the entire group. Only 14 students had baseline Lp(a) levels above 5.0 mg/dl (lower limit of detectability of the assay) and in this subset, the mean Lp(a) level increased significantly (22.7 vs 17.0 mg/dl, 33.5% increase, P < 0.022). Students exercised less during examinations (2.1 + 3.0 vs 4.4+ 5.1 h/week, P
MODIFIED LIPOPROTEINS
1138j Effects of water-soluble
plasma antioxidants on LDL oxidation USE, Leake DS, Dept. of Biochem. and Physiol., Univ. of Reading, Berkshire, RG6 2AJ, UK
It is generally believed that large-scale LDL oxidation does not occur within the circulation because of the antioxidant capacity of plasma. We have investigated the effects of various water-soluble plasma antioxidants on LDL oxidation. Human LDL (lOOpug protein /ml) was incubated with mouse resident peritoneal macrophages for 18 h at 37°C in Ham’s F-10 medium containing 6,uM iron and various concentrations of the antioxidant under study. The degradation and uptake of the LDL by 3774 macrophages was then measured. Macrophage-oxidized LDL was taken up by 5774 macrophages 3-10 times faster than control LDL. Lipoprotein-deficient fetal calf serum (5%) almost totally inhibited the oxidation of LDL. 50% inhibition of LDL oxidation was achieved with 4 g albumin/i, 2pM bilirubin, 0.75 PM apo-transferrin and 45-60pM ascorbate. 50 g albumin/l, 7.5 PM bilirubin, 3 PM apo-transfenin and 60-1OOpM ascorbate resulted in total, or near total, inhibition. The average plasma concentrations of these antioxidants are 40 g/l, 8.5pM, 30,~M and 20-55pM respectively. Holotransferrin. which is saturated with iron, was unable to inhibit LDL oxidation by macrophages, indicating that apo-transferrin must inhibit LDL oxidation by binding the iron ions in the medium that are essential for the modification of the LDL. These results support the belief that large-scale LDL oxidation is unlikely to occur within the circulation. 11391 Zinc can either increase or decrease LDL oxidation . m Leake DS, Dept. of Biochem. and Physiol., Univ. of Reading, Be&hire, RG6 ZAJ. UK We have investigated
the effect of zinc ions on iron-dependent
oxidation of LDL in vitro, because of its potential effects on atherosclerosis. Atherosclerotic lesions may well be acidic and so we have used buffers of various pHs. Human LDL was incubated for 18 h at 37°C in Ham’s F-10 medium (pH 7.4) or modified Hanks’ balanced salt solution (HBSS) at pH 7.4, 6.5 or 5.5 in the presence of 6yM Fe2” and cysteine (5OOyM in Ham’s F-10 or 1OOpM in HBSS). LDL oxidation was assayed by measuring hydroperoxides, thiobarbituric acid reactive-substances and uptake by 5774 macrophages. Zinc caused a dose-dependent inhibition of LDL oxidation in Ham’s F-10, with a half-maximal inhibition at l-3 PM. (In other experiments, Zn*+ also inhibited LDL oxidation by macrophages or endothelial cells in Ham’s F-10 medium.) LDL oxidation in HBSS increased with decreasing pH. At each pH, Zn2+ (up to increase in LDL oxida1OpM) caused a large dose-dependent tion. In Ham’s F-10, the antioxidant effect of zinc may possibly be explained by the displacement of iron from its binding sites on LDL, hence reducing the local oxidative stress. In HBSS, a much simpler buffer system, Zn2+ may increase LDL oxidation possibly by displacing iron from the phosphate ions making the iron more available. These results may help to explain why it is very unclear whether zinc is pro- or anti- atherogenic in vivo.
1
High density lipoproteins have antioxidative activity in vivo
WAN,
Gurevich VS, Nikiforova AA, Denisenko AD, Kuznetsov AS, Shatilina LV, Plavinsky SL, Dept. qf Biochem., Inst. of Exp. Med., 12 Acad. Pavlov Str., St. Petersburg 197376, Russia
It is known that addition of HDL to a solution of LDL slows down the formation of lipid peroxide products, both spontaneous and induced by iron and copper ions, xanthine-xantbine oxidase or endothelial cells. The question arises whether HDLs exert a
Atherosclerosis X, Montreal, October I994