Ratio Of Low-density Lipoprotein Research Articles

The effect of fatty acid composition of rapeseed oil on plasma lipids and oxidative stability of low-density lipoproteins in cholesterol-fed hamsters

We studied the effect of four rapeseed oils with different fatty acid profiles on parameters implicated in the pathogenesis of atherosclerosis in humans in a model experiment with hamsters. The hamsters were divided into seven groups and fed a semi-synthetic, cholesterol-enriched diet (5 g/kg diet) containing 15% of the fat in question for a period of six weeks. The following rapeseed oils were used: (1) conventional rapeseed oil (6% saturated fatty acids [SFA], 64% monounsaturated fatty acids [MUFA], 18% linoleic acid [LA], 9% α-linolenic acid [ALA]), (2) linoleic acid-rich rapeseed oil (6% SFA, 61% MUFA, 28% LA, 2% ALA), (3) oleic acid-rich rapeseed oil (6% SFA, 74% MUFA, 11% LA, 5% ALA), (4) myristic acid-rich rapeseed oil (11% myristic acid, 35% SFA, 44% MUFA, 14% LA, 5% ALA). Sunflower oil, olive oil and lard were used as control fats. The concentrations of the lipids in the plasma, in the lipoprotein fractions and in the liver, the fatty acid composition of various tissues, the tocopherol status and the susceptibility of low-density lipoproteins (LDL) to in vitro-oxidation were determined. The concentrations of total cholesterol found in the plasma and in the LDL fraction and the ratios of LDL to HDL were similar after feeding the four different types of rapeseed oil, sunflower oil and olive oil. Lard produced the highest concentrations of cholesterol in plasma and the LDL fraction and the highest ratio of LDL to HDL. Feeding conventional, oleic acid- and myristic acid-rich rapeseed oils resulted in markedly lower ratios of arachidonic to eicosapentaenoic acid in the lipids of the liver and the erythrocytes. This is considered beneficial for the formation of eicosanoids. The lag-time before the onset of peroxidation of the LDL lipids, induced by copper ions, was not statistically significant between the seven hamster groups suggesting that the susceptibility of LDL to lipid peroxidation was similar after feeding all types of fat. Considering all parameters obtained in the used hamster model it is obvious that all four rapeseed oils are at least as favourable as olive oil or sunflower oil.

Gene dose effect of the APOE-epsilon4 allele on plasma HDL cholesterol level in patients with Alzheimer's disease.

It has been reported that decreased serum high density lipoprotein (HDL) cholesterol level is related with severity of Alzheimer's disease (AD). Here, 82 patients with AD and 40 non-demented individuals were examined to determine how the APOE-epsilon4 allele modifies plasma cholesterol fractions. In adjusting for age, sex and plasma albumin level, plasma HDL cholesterol level was inversely correlated with the APOE-epsilon4 dose only in the patients (P = 0.0048), while plasma low density lipoprotein (LDL) cholesterol level tended to be correlated with the APOE-epsilon4 dose in both groups, although this was not significant. The ratio of LDL to HDL cholesterol in the patients showed a similar correlation with the APOE-epsilon4 dose to that in the controls, and this correlation was evident (P = 0.0069) after putting all subjects into one group. However, neither HDL nor LDL cholesterol levels showed significant differences between the groups. These results indicated that the APOE-epsilon4 dose affects the composition of plasma cholesterol, and suggested that the genetic effect on plasma lipid metabolism could be distinctive in patients with AD.

Lipolytic enzyme effect on small low-density lipoprotein particles in women treated with estrogen

Objective: To test whether hydrolysis of low-density lipoprotein (LDL) triglyceride by lipolytic enzymes decreases the size of LDL particles in women treated with estrogen replacement. Methods: Fifteen postmenopausal women received 0.625 mg conjugated equine estrogens daily for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also assayed levels of total, free, and esterified cholesterol, triglyceride, and protein in LDL. Plasma samples were incubated at 37C for 24 hours and LDL fractions were isolated by ultracentrifugation. After LDL samples were further incubated with or without lipoprotein lipase (500, 700, and 1000 ng/mL) at 37C for 24 hours, LDL triglyceride, LDL protein, and the diameter of LDL particles were measured. Results: Estrogen decreased total cholesterol and increased triglyceride and HDL cholesterol in plasma. Estrogen treatment decreased the ratio of cholesteryl ester/protein, whereas the ratio of triglyceride/protein increased. Estrogen decreased LDL particle diameter. Incubation of plasma increased the ratio of LDL triglyceride/protein from 0.40 ± 0.14 to 0.48 ± 0.15 ( P < .05) and decreased the ratio of LDL cholesteryl ester/protein from 1.17 ± 0.25 to 1.09 ± 0.22 ( P < .05), but LDL particle diameter did not change. Incubation of LDL with lipoprotein lipase reduced the LDL triglyceride/protein ratio, and decreased the diameter of LDL particles from 25.61 ± 0.87 nm to 24.89 ± 0.88 nm (500 ng/mL, P < .05), 24.62 ± 1.20 nm (700 ng/mL, P < .05), and 24.67 ± 1.19 nm (1000 ng/mL, P < .05). Conclusion: In women treated with estrogen, hydrolysis of triglyceride in LDL particles might be accompanied by reduced particle size.

Sialic acid content of low-density lipoprotein in women with coronary artery disease

A low sialic acid content in low-density lipoprotein (LDL) has been associated with coronary artery disease (CAD) in studies that have included mostly male subjects. We compared the sialic acid–to–apolipoprotein B ratios of total LDL and its subfractions in middle-aged women with CAD (CAD+, n = 22) with those ratios in healthy female control subjects (CAD–, n = 11). CAD+ subjects had a lower sialic acid ratio in total LDL and in its subfractions as compared with results in CAD– subjects. In total, light, and dense LDL, the sialic acid ratio was negatively correlated with the respective cholesterol and phospholipid concentrations, and in very dense LDL, it was negatively correlated with triglyceride concentration. In multivariate analysis, CAD and LDL cholesterol contributed to the explanation of the variability of LDL sialic acid ratios. In summary, a low sialic acid–to–apolipoprotein B ratio in LDL was associated with the presence of CAD in middle-aged women with mild to moderate hypercholesterolemia. (J Lab Clin Med 2000;136:110-5)

Statin treatment increases the sialic acid content of LDL in hypercholesterolemic patients

Low density lipoprotein (LDL) with low sialic acid content has been reported to cause intracellular cholesterol accumulation, and therefore desialylation has been proposed to be an atherogenic modification of LDL. However, it is not known whether hypolipidemic treatment has any effect on LDL sialylation. Accordingly, we investigated the sialic acid/apolipoprotein (apo) B ratio of total LDL and its subfractions in 26 moderately hypercholesterolemic patients at baseline and after treatment with statins for 2–3 months. Cholesterol and triglyceride levels were reduced in all apo B-containing lipoproteins, including all LDL subfractions, while the sialic acid ratio was increased in total LDL and in all its subfractions. Cholesterol concentrations and sialic acid ratios were inversely correlated in light and dense LDL subfractions both before and during statin treatment, and the greater the decrease in cholesterol and apo B contents of dense LDL, the higher was the increase in its sialic acid ratio. Furthermore, the lower the baseline sialic acid ratio of dense LDL, the greater was the reduction in its lipid and apo B concentrations. In conclusion, inhibition of cholesterol synthesis by statin treatment increased sialic acid/apo B ratio in LDL proportionately to the decrease of LDL apo B and cholesterol.

Sialic acid content of low density lipoprotein and its relation to lipid concentrations and metabolism of low density lipoprotein and cholesterol

A low sialic acid content in low density lipoprotein (LDL) has been associated with atherogenicity and coronary artery disease (CAD) in many but not all studies. We investigated associations of the sialic acid-to-apolipoprotein B (apoB) ratio of LDL with lipoprotein lipid concentrations, kinetics of LDL, metabolism of cholesterol, and the presence of CAD in 98 subjects (CAD+, n = 56; CAD−, n = 42). The sialic acid ratios of total, dense, and very dense LDL were lower in the CAD+ than CAD− subjects, especially at high sialic acid ratios. The LDL sialic acid ratio was inversely associated with respective lipid and apoB concentrations and positively with lipid-to-apoB ratios of LDL. The transport rates (TRs) for total and dense LDL apoB were negatively associated with their sialic acid ratios. The sialic acid ratio of dense LDL, but not that of total LDL, was inversely correlated with serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, and positively with serum levels of plant sterols, indicators of cholesterol absorption. In addition, the TR for dense LDL was positively correlated with cholesterol synthesis.In conclusion, a low LDL sialic acid ratio was associated with CAD, high numbers of small LDL particles, and a high TR for LDL apoB, and in dense LDL also with high synthesis and low absorption of cholesterol.

Lipid Transfer Reactions and Lipid Composition of Low-Density Lipoprotein Particles in Postmenopausal Women Receiving Estrogen

In Brief Objective To investigate the effects of estrogen on lipid transfer reactions and lipid composition of low-density lipoprotein (LDL) particles in postmenopausal women. Methods Twelve postmenopausal women were treated with conjugated equine estrogen, 0.625 mg daily, for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also determined the amount of total, free, and esterified cholesterol, triglyceride, and apolipoprotein B in LDL. To evaluate lipid transfer reactions, plasma samples were incubated at 37C for 24 hours, and replacement of cholesteryl ester by triglyceride in LDL particles was analyzed. Cholesterol and triglyceride concentrations were measured enzymatically. Apolipoprotein B concentrations were determined by an immunoturbidimetric assay. Results Estrogen significantly reduced the plasma levels of total cholesterol and significantly increased those of triglyceride and HDL cholesterol. The ratio of cholesteryl ester to apolipoprotein B was reduced significantly, whereas the ratio of triglyceride to apolipoprotein B increased significantly after estrogen treatment. Both before and after estrogen treatment, incubation of plasma induced a significant increase in the ratio of LDL-triglyceride to apolipoprotein B with a concomitant decrease in the ratio of LDL–cholesteryl ester to apolipoprotein B. Incubation-induced changes in these ratios were significantly enhanced by estrogen therapy. The plasma concentration of triglyceride was correlated positively with incubation-induced changes in the ratio of LDL-triglyceride to apolipoprotein B (r = .83, P < .001) and correlated negatively with changes in the ratio of LDL–cholesteryl ester to apolipoprotein B (r = −.61, P < .01). Conclusion Estrogen-induced increase in the plasma level of triglyceride may enhance lipid transfer reactions, resulting in triglyceride-rich and cholesteryl ester-poor LDL particles. An increase in plasma triglyceride levels induced by estrogen therapy may enhance lipid transfer reactions, resulting in triglyceride-rich and cholesteryl ester–poor low-density lipoprotein particles in postmenopausal women.

Lipid transfer reactions and lipid composition of low-density lipoprotein particles in postmenopausal women receiving estrogen

Objective: To investigate the effects of estrogen on lipid transfer reactions and lipid composition of low-density lipoprotein (LDL) particles in postmenopausal women. Methods: Twelve postmenopausal women were treated with conjugated equine estrogen, 0.625 mg daily, for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also determined the amount of total, free, and esterified cholesterol, triglyceride, and apolipoprotein B in LDL. To evaluate lipid transfer reactions, plasma samples were incubated at 37C for 24 hours, and replacement of cholesteryl ester by triglyceride in LDL particles was analyzed. Cholesterol and triglyceride concentrations were measured enzymatically. Apolipoprotein B concentrations were determined by an immunoturbidimetric assay. Results: Estrogen significantly reduced the plasma levels of total cholesterol and significantly increased those of triglyceride and HDL cholesterol. The ratio of cholesteryl ester to apolipoprotein B was reduced significantly, whereas the ratio of triglyceride to apolipoprotein B increased significantly after estrogen treatment. Both before and after estrogen treatment, incubation of plasma induced a significant increase in the ratio of LDL-triglyceride to apolipoprotein B with a concomitant decrease in the ratio of LDL–cholesteryl ester to apolipoprotein B. Incubation-induced changes in these ratios were significantly enhanced by estrogen therapy. The plasma concentration of triglyceride was correlated positively with incubation-induced changes in the ratio of LDL-triglyceride to apolipoprotein B ( r = .83, P < .001) and correlated negatively with changes in the ratio of LDL–cholesteryl ester to apolipoprotein B ( r = −.61, P < .01). Conclusion: Estrogen-induced increase in the plasma level of triglyceride may enhance lipid transfer reactions, resulting in triglyceride-rich and cholesteryl ester-poor LDL particles.

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (< 7% of total energy from saturated fat), low-cholesterol (< 80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% ± 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% ± 1.7%, P < .001), apolipoprotein B (8.2% ± 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% ± 2.0%, P = .004) and apolipoprotein B to A-I (5.4% ± 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.

Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women.

In order to investigate the effect of a short-term application of marine n-3 polyunsaturated fatty acids on the composition of serum very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), nine women aged 29 +/- 4.2 years, following a diet with a SFA/MUFA/PUFA profile of 2.4/3/1, received supplements of six capsules daily, each capsule containing 0.137 g of n-3 fatty acids (14.5% eicosapentaenoic acid (EPA) and 8.9% docosahexaenoic acid (DHA)) for 10 d. Food consumption, assessed during two 10-days periods indicates that percentage contribution of SFA, MUFA, and PUFA to the daily energy intake did not change through the fish-oil supplementation period, but the daily consumption of n-3 fatty acids increased 2.3 times. N-3 fatty supplementation increased EPA and DHA percentages in serum phospholipids, but failed to decrease (p > 0.05) the cholesterol and triglyceride concentration in serum LDL and HDL, although it did so in VLDL. In contrast, the lipoprotein-phospholipid and lipoprotein-protein concentrations were markedly affected, mainly in LDL and HDL (at least p < 0.01). HDL and VLDL compositions were not affected but the total mass (lipid + protein in mg/dl) concentration of these lipoproteins significantly decreased (p < 0.05), suggesting a lower number of these particles in circulating blood after the n-3 treatment. The LDL-cholesterol/LDL-apolipoprotein B ratio increased (p < 0.01) reflecting a probable increase in LDL size. Following fish oil supplementation, LDL particles contained a significantly lower amount of phospholipids, which also suggests changes in the surface/core ratio of the average LDL. Changes in serum lipoprotein lipids did not significantly correlate with any dietary change other than the n-3 fatty acid increase. The results indicate that a 10-day application of a small supplement of n-3 change the LDL composition leading to less atherogenic LDL particles with lower phospholipid and apolipoprotein (Apo) B concentrations.

The Effect of a Pure Antiandrogen Receptor Blocker, Flutamide, on the Lipid Profile in the Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

The Effect of a Pure Antiandrogen Receptor Blocker, Flutamide, on the Lipid Profile in the Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

Effects of l-Triiodothyronine and the Thyromimetic L-94901 on Serum Lipoprotein Levels and Hepatic Low-Density Lipoprotein Receptor, 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase, and Apo A-I Gene Expression

The mechanisms by which thyroid hormone (triiodothyronine (T 3)) and a thyromimetic, 2-amino-3-(3,5-dibromo-4-[4-hydroxy-3-(6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenoxyl]-phenyl)-propionic acid (L-94901), lower plasma low density lipoprotein (LDL) cholesterol and raise plasma high density lipoprotein (HDL) cholesterol levels was investigated in thyroidectomized and sham-operated rats. Thyroidectomy resulted in a 77% increase in plasma LDL cholesterol, a 60% decrease in plasma triglycerides, and a modest reduction in HDL cholesterol. Daily oral dosing with T 3 (10–170 nmol/kg) or L94901 (100–1000 nmol/kg) for 7 days decreased plasma LDL cholesterol in thyroidectomized rats by 60–80%, respectively. This reduction in LDL cholesterol was accompanied by a dose-dependent increase in HDL cholesterol levels of up to 60%. Thus, the ratio of LDL to HDL was decreased from 1.01 to 0.12 after treatment with L-94901 and to 0.25 after dosing with T 3. In sham-operated animals, T 3 and L-94901 lowered LDL cholesterol by 61 and 46%, respectively, and increased HDL cholesterol by 25 and 53%, respectively. Immunoblotting analysis of liver membranes prepared from thyroidectomized or sham-operated rats demonstrated that LDL receptor protein levels were increased by up to eight-fold. Northern blotting analysis revealed similar large increases in hepatic LDL receptor mRNA levels that accounted for the increases in LDL receptor protein levels. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA, protein, and activity were increased 2- to 3-fold. The T 3- and L-94901-mediated increases in serum HDL levels were associated with 2- to 3-fold increases in apo A-I mRNA levels. In contrast with most other hypocholesterolemic agents, T 3 and L-94901 significantly increase HDL cholesterol levels in addition to decreasing LDL cholesterol levels due to induction of hepatic apo A-I and LDL receptor gene expression.

Associations of indices of adiposity with atherogenic lipoprotein subfractions.

To investigate the associations of indices of adiposity with cardiovascular risk factors. 93 men and 98 women aged 18-69 y. Body mass index (BMI), waist to hip ratio (WHR), waist circumference, waist to height ratio, blood pressure, fasting concentrations of blood glucose, insulin, plasma lipids and lipoprotein subfractions, apoproteins, lipoprotein(a) and post-heparin lipases. BMI and waist showed similar associations (P < 0.01) with a cluster of major cardiovascular risk factors including total cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in men, and ratio of low density lipoprotein-/high density lipoprotein-cholesterol for both genders. Large waist circumference was significantly (P < 0.01) associated (controlled for age and smoking) with features of the metabolic syndrome, including raised insulin concentration (men: r=0.37, women: r=0.49), reduced high density lipoprotein2 (men: r=-0.30, women: r=-0.34), increased very low density lipoprotein1 mass (men: r=0.31, women: r=0.42), raised small, dense low density lipoprotein (men: r=0.30, women: r=0.31), elevated blood pressure (men: r=0.27, women: r=0.28), increased triglyceride (men: r=0.43, women: r=0.48) and apolipoprotein-B (men: r=0.32, women: r=0.35). Waist circumference also correlated with hepatic lipase/lipoprotein lipase ratio in women (r=0.52). Height adjustment did not substantially change relationships between waist circumference and risk factors. WHR correlated with fewer risk factors. For the purpose of health promotion to prevent cardiovascular disease associated with overweight and intra-abdominal fat accumulation, the general public should be advised to be aware of the risk associated with large waist circumference.

Effect of infusion of a triacylglycerol emulsion on low-density lipoprotein composition and oxidizability

Six, healthy, male volunteers aged 19–48 years received a 4-h infusion of a triacylgycerol emulsion (Intralipid 10%) after an overnight fast. Plasma triacylglycerol (TAG) and low-density lipoprotein (LDL) -TAG, -protein and -phospholipid concentrations all rose significantly during the course of the infusion and remained elevated 90 min after its end. The weight/weight ratio of LDL–TAG to -protein also increased significantly (from 0.43±0.14 to 0.79±0.30 at 4 h and 0.63±0.31 90 min later), indicating TAG-enrichment of LDL particles. There were no significant changes in LDL particle density. Susceptibility of LDL to copper-induced oxidation, as measured by the lag time for conjugated diene formation, was less at the end of and 90 min after the end of the infusion than in the fasting state (59.3±16.5, 47.4±17.4 and 34.8±19.6 min, respectively). Lag time was positively correlated with LDL–TAG in the fasting state ( r s=0.900, P<0.0001) and the correlation continued with the post-infusion TAG-enriched LDL ( r s=0.886, P<0.05). Acute hypertriglyceridaemia induced by infusion of Intralipid therefore causes TAG-enrichment and a decrease in the susceptibility to oxidation of LDL. TAG-enrichment of LDL may lead to subsequent potentially atherogenic changes in LDL following TAG hydrolysis.

Oxidation of Free Fatty Acids in Low Density Lipoprotein by 15-Lipoxygenase Stimulates Nonenzymic, α-Tocopherol-mediated Peroxidation of Cholesteryl Esters

15-Lipoxygenase has been implicated in the in vivo oxidation of low density lipoprotein (LDL) a process thought to be important in the origin and/or progression of human atherogenesis. We have suggested previously that oxidation of LDL's cholesteryl esters (CE) and phospholipids by soybean (SLO) or human recombinant 15-lipoxygenase (rhLO) can be ascribed largely to alpha-tocopherol (alpha-TOH)-mediated peroxidation (TMP). In this study we demonstrate that addition to LDL of unesterified linoleate (18:2), other free fatty acid (FFA) substrates, or phospholipase A2 (PLA2) significantly enhanced the accumulation of CE hydro(pero)xides (CE-O(O)H) induced by rhLO, whereas the corresponding CE and nonsubstrate FFA were without effect. The enhanced CE-O(O)H accumulation showed a dependence on the concentration of free 18:2 in LDL. In contrast, addition of 18:2 had little effect on LDL oxidation induced by aqueous peroxyl radicals or Cu2+ ions. Analyses of the regio- and stereoisomers of oxidized 18:2 in SLO-treated native LDL demonstrated that the small amounts of 18:2 associated with the lipoprotein were oxidized enzymically and within minutes, whereas cholesteryl linoleate (Ch18:2) was oxidized nonenzymically and continuously over hours. alpha-Tocopheroxyl radical (alpha-TO.) formed in LDL exposed to SLO was enhanced by addition of 18:2 or PLA2. With rhLO and 18:2-supplemented LDL, oxidation of 18:2 was entirely enzymic, whereas that of Ch18:2 was largely, though not completely, nonenzymic. The small extent of enzymic Ch18:2 oxidation increased with increasing enzyme to LDL ratios. Ascorbate and the reduced form of coenzyme Q, ubiquinol-10, which are both capable of reducing alpha-TO. and thereby preventing TMP, inhibited nonenzymic Ch18:2 oxidation induced by rhLO. Trolox and ascorbyl palmitate, which also inhibit TMP, ameliorated both enzymic and nonenzymic oxidation of LDL's lipids, whereas probucol, a radical scavenger not capable of preventing TMP, was ineffective. These results demonstrate that rhLO-induced oxidation of CE is largely nonenzymic and increases with LDL's content of FFA substrates. We propose that conditions which increase LDL's FFA content, such as the presence of lipases, increase 15-LO-induced LDL lipid peroxidation and that this process requires only an initial, transient enzymic activity.

Oxidation of low-density lipoproteins produces levuglandin-protein adducts.

Free-radical oxidation of human low-density lipoprotein (LDL) produces levuglandin (LG)-protein adducts that were detected with an enzyme-linked immunosorbent assay using LGE2-KLH antibodies which recognize LGE2-derived pyrroles. The level of immunoreactivity increases with time of oxidation and reaches a maximum by 8 h. The yield of pyrrole varies nonlinearly with the level of LG adduction to LDL. At low LG:LDL ratios, such as those detected in oxidized LDL, the reaction of primary amino groups with LGE2 produces mostly non-pyrrole adducts that are not immunoreactive. Concomitant phospholipolysis must occur if the generation of immunoreactive epitopes in LDL involves oxidation of arachidonyl phospholipids. Thus, since a protein adduct prepared from synthetic LGE2-2-lysophosphatidylcholine ester showed, at most, only 0.5% cross-reactivity with the LGE2-KLH antibodies, the epitopes detected in oxidized LDL are almost certainly not protein adducts of LG-phospholipid esters. As expected, hydrolysis of the carboxylic ester in the protein adduct of LGE2-2-lysophosphatidylcholine ester by treatment with phospholipase A2 produced a fully immunoreactive LGE2-protein adduct.

Effect of psyllium in hypercholesterolemia at two monounsaturated fatty acid intakes

We performed two studies to determine whether the lipid-lowering effect of viscous soluble fiber was modified by monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ) was compared with wheat bran (control) in 1-mo metabolic diets by using a randomized crossover design (n = 32 hyperlipidemic subjects). The background diet contained approximately 6% of energy as MUFA (20% of total fat). The second study (n = 27 hyperlipidemic subjects) was similar to the first but the background diet contained approximately 12% MUFA (29% of total fat) because of the addition of canola oil. At both fat intakes, psyllium resulted in significant reductions in total, low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol compared with the wheat bran control. For the psyllium diet at 6% compared with 12% MUFA, the decreases in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3 +/- 2.4% (P < 0.001), respectively. With the higher-MUFA diet triacylglycerol fell significantly over the control phase (16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL cholesterol fell significantly over the psyllium phase (7.3 +/- 2.8%, P = 0.015). Psyllium and MUFA intakes were negatively related to the percentage change in the ratio of LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P = 0.002, respectively). Chenodeoxycholate synthesis rate increased (30 +/- 13%, P = 0.038) with the psyllium diet in the 12 subjects in whom this was assessed. We conclude that psyllium lowered LDL- and HDL-cholesterol concentrations similarly at both MUFA intakes. However, there may be some advantage in combining soluble fiber and MUFA to reduce the ratio of LDL to HDL cholesterol.

Relation of smoking at baseline and during trial years 1–6 to food and nutrient intakes and weight in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial

This chapter describes dietary composition according to cigarette smoking status at baseline and changes in smoking status during follow-up for men in the special intervention (SI) and usual care (UC) groups of the Multiple Risk Factor Intervention Trial. Five patterns of smoking behavior were defined: 1) sustained nonsmoking, 2) early (years 1-2 of the trial) sustained quitting, 3) late (years 3-6 of the trial) sustained quitting, 4) recidivism, and 5) continued smoking. SI men who quit smoking showed greater favorable changes in dietary lipid composition and micronutrient intake than did continued smokers, and these changes were in many instances as great as favorable changes made by nonsmokers. On the other hand, SI men who quit smoking gained an average of 3.8 lb (1.7 kg), in contrast with nonsmokers who lost an average of 6.4 lb (2.9 kg). The gain by SI quitters was, however, less than that by UC quitters, who gained 6.5 lb (3.0 kg). Moreover, despite weight gain, net change in high-density-lipoprotein (HDL) cholesterol for SI quitters was positive. With the associated decrease in low-density-lipoprotein (LDL) cholesterol, early SI quitters had the most improvement in ratio of LDL to HDL among all subgroups. Thus, unfavorable nutritional patterns of smokers put them at double jeopardy regarding cardiovascular and other chronic diseases; additionally, long-term risks can be improved not only by smoking cessation but also by achievement of healthier eating patterns.