Normolipemic Subjects Research Articles

Effect of simvastatin in familial hypercholesterolemia on the affinity of electronegative low-density lipoprotein subfractions to the low-density lipoprotein receptor

The effect of simvastatin therapy on the biologic characteristics of the electronegative low-density lipoprotein (LDL) subfraction of patients with familial hypercholesterolemia (FH) was studied. Total LDL, isolated from FH plasma at 0, 3 and 6 months of simvastatin treatment, was subfractionated into electropositive LDL (LDL[+]) and electronegative LDL (LDL[−]) by anion exchange chromatography. LDL isolated from healthy normolipemic (NL) subjects was used as a control. The LDL(−) proportion was twofold higher in patients with FH than in NL subjects (17.6 ± 1.6% vs 7.8 ± 1.5%, respectively; p <0.05) and was progressively reduced by simvastatin therapy (15.7 ± 1.6% at 3 months; 13.8 ± 2.5% at 6 months; p <0.05). Both LDL subfractions from patients with FH had a higher relative cholesterol content and decreased apolipoprotein B and triglycerides than NL subfractions. Simvastatin progressively induced changes in lipid content of both LDL subfractions in patients with FH, and lipid composition was closer to these subfractions in NL subjects after 6 months of therapy. Binding displacement experiments in human fibroblasts demonstrated that LDL(−) from both groups of subjects had a lower affinity of binding to the LDL receptor that LDL(+). In addition, LDL(+) in patients with FH presented an intermediate binding affinity between LDL(−) and LDL(+) in NL subjects. Simvastatin-induced changes in LDL composition were accompanied by a progressive increase in affinity of LDL(+) and LDL(−) in patients with FH. After 6 months of therapy, LDL(+) in FH had an affinity similar to that of LDL(+) in NL subjects. The LDL(−)-induced release of chemokines interleukin-8 and monocyte chemotactic protein-1 from cultured endothelial cells was twofold higher compared with that of LDL(+). No difference in chemokine release between patients with FH and NL subjects or the effect of simvastatin were observed. We conclude that simvastatin therapy was able to modify LDL subfraction composition in subjects with FH and increase their affinity to the LDL receptor. This improvement could contribute to the observed reduction in LDL(−) proportion induced by simvastatin.

Effect of genistein against copper-induced lipid peroxidation of human high density lipoproteins (HDL)

Several studies have demonstrated that the isoflavone genistein exerts a protective effect against lipid peroxidation of low density lipoproteins (LDL). Aim of our study was to investigate whether genistein protects high density lipoproteins (HDL), isolated from normolipemic subjects, against Cu ++-induced lipid peroxidation. Our results demonstrated that genistein exerts an inhibitory effect against Cu ++-induced lipid peroxidation of HDL, as shown by the lower increase in the levels of conjugated dienes in lipoproteins oxidized after preincubation with different concentrations of genistein (0.5–2.5 μM). Moreover the analysis of fluorescence emission spectra of tryptophan (Trp) and Laurdan (6-dodecanoyl-2-dimethyl-aminonaphthalene) demonstrated that genistein prevents the alterations of apoprotein structure and physico-chemical properties, associated with Cu ++-triggered lipid peroxidation of lipoproteins. The protective effect exerted by genistein against oxidative damage of lipoproteins was realized at concentrations similar to those observed in plasma of human subjects consuming a traditional soy diet or receiving a soy supplement. Therefore, we suggested that antioxidant activity exerted by genistein against lipid peroxidation of HDL in vitro could be of physiological relevance.

Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins

In the present study, we confirmed that copper ions induce oxidative damage in human astrocytes in culture, as demonstrated by the significant increase in the levels of hydroperoxides and in the fluorescence intensity of the fluorescent probe dichloro-dihydrofluorescein diacetate (H 2DCFDA). The compositional changes were associated with a significant decrease in cell viability in astrocytes treated with 10 μM Cu ++ with respect to control cells. Astrocytes incubated with copper ions in the presence of high density lipoproteins (HDL) isolated from plasma of normolipemic subjects showed lower levels of hydroperoxides and a higher cell viability with respect to cells oxidized alone. Moreover, a significant decrease in the levels of hydroperoxides was observed in oxidized astrocytes treated with HDL. These results demonstrate that HDL exert a protective role against lipid peroxidation. The protective effect could be related to the ability of HDL to bind metal ions at the lipoprotein surface and/or to a stimulation of the efflux of lipid hydroperoxides from cell membranes as demonstrated in other cell types. Oxidative damage of astrocytes was induced at a copper concentration similar to that observed in cerebrospinal fluid (CSF) of patients affected by neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's diseases (PD). Lipoprotein particles similar for density and chemical composition to plasma HDL were recently isolated in human CSF, therefore, the protective role exerted by HDL against Cu ++-induced oxidative damage of astrocytes could be of physiological relevance.

Electronegative LDL of FH subjects: chemical characterization and induction of chemokine release from human endothelial cells

Electronegative LDL (LDL(−)) constitutes a plasma subfraction of LDL with proinflammatory properties. Its proportion is increased in familial hypercholesterolemia (FH); however, the characteristics of LDL(−) isolated from FH subjects have not been previously studied. In this work, the composition, oxidative status, and inflammatory capacity on endothelial cells of LDL(−) from FH and normolipemic (NL) subjects were evaluated. LDL(−) from FH was relatively enriched in esterified and free cholesterol and triglyceride, and had lower apoB and phospholipid content compared with the non-electronegative fraction (LDL(+)). LDL(−) also contained increased amounts of apoE, apoC-III, sialic acid, and non-esterified fatty acids (NEFAs). The same was observed in NL subjects, except that esterified cholesterol and phospholipid were similar in LDL(−) and LDL(+). No difference was observed between the two fractions concerning malondialdehyde, fatty acid hydroxides, and antioxidants, thereby indicating the absence of increased oxidation of LDL(−) compared with LDL(+). When LDL(−) (100 mg/l) from NL and FH subjects was incubated for 24 h with human umbilical vein endothelial cells (HUVECs), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) increased twofold in the culture medium compared with LDL(+). Vascular cell adhesion molecule 1 (VCAM-1) expression was not increased by LDL(−). Our data indicate that LDL(−) from FH or NL subjects shows no evidence of increased oxidative modification compared to LDL(+); however, LDL(−) induces twofold the release of chemokines by endothelial cells. This effect, which may contribute to leukocyte recruitment and promote atherogenesis, may be greater in FH subjects in which LDL(−) can be up to eightfold higher than in NL subjects.

Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects

Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects

This month in J Lab Clin Med: Issue highlights for January 2003

This month in J Lab Clin Med: Issue highlights for January 2003

Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects

The density distribution of electronegative LDL [LDL(−)], a cytotoxic and inflammatory fraction of LDL present in plasma, was studied in 10 normolipemic (NL), 6 FH, and 11 hypertriglyceridemic (HTG) subjects. Six LDL subclasses of increased density (LDL1 to LDL6) were isolated by density-gradient ultracentrifugation (DGU). NL and FH subjects showed prevalence of light LDL, whereas HTG subjects showed prevalence of dense LDL. LDL(−) proportion was determined from total LDL or LDL-density subclasses by anion-exchange chromatography. LDL from FH patients had increased LDL(−) (35.1 ± 9.9%) compared with LDL from NL and HTG subjects (9.4 ± 2.3% and 12.3 ± 4.3%, respectively). Most LDL(−) was contained in dense subclasses in NL (LDL4–6, 67.7 ± 3.1%) whereas most of LDL(−) from FH patients were contained in light LDL subclasses (LDL1–3) (86.2 ± 1.6%). In these subjects, simvastatin therapy decreased LDL(−) to 28.2 ± 6.7% and 21.2 ± 5.6% at 3 and 6 months of treatment, respectively, due mainly to decreases in light LDL subclasses. In HTG subjects, half LDL(−) was contained in dense LDL subclasses (LDL4–6, 46.1 ± 2.0%). Non-denaturing acrylamide gradient gel electrophoresis concurred with DGU data, as LDL(−) from NL showed a single band of lower size than non-electronegative LDL [LDL(+)], whereas LDL(−) from FH and HTG presented bands of greater size than its respective LDL(+). These results reveal the existence of light and dense LDL(−), indicate that hyperlipemia could promote the formation of light LDL(−) and suggest that LDL(−) could have different origins.—Sánchez-Quesada, J. L., S. Benítez, C. Otal, M. Franco, F. Blanco-Vaca, and J. Ordóñez-Llanos. Density distribution of electronegative LDL in normolipemic and hyperlipemic subjects. J. Lipid Res. 2002. 43: 699–705.

Relationship between serum complement and different lipid disorders.

Inflammatory and lipid factors share an important role in atherosclerosis. Recent studies showed the concomitant presence and increase of complement components and lipids both in the atherosclerotic plaque and the circulating blood. The aim of this study was to examine the relationship between the complement system and lipid disorders. We evaluated the circulating complement terminal complex C5b-9, a clear sign of complement activation, in three groups of 30 patients the first with hypercholesterolemia, the second with hypertriglyceridemia (associated with low values of HDL-cholesterol), the third with low levels of HDL-cholesterol compared with an equivalent group of matched normolipemic subjects. We found a significant increase of sC5b-9 in each group of patients compared with controls. The mean sC5b-9 level in the hypercholesterolemic population was 366.2 +/- 141.2 ng/ml (P<0.01), 395.4 +/- 118.2 ng/ml in the hypertrygliceridemic group (P<0.01), 414.8 +/- 126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0 +/- 40.8. ng/ml in the control group. Regression analysis showed a significant direct correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse correlation between sC5b-9, HDL-chol (r=-0.74), and apo-A1 (r=-0.68); no significant relationship was found between sC5b-9 and cholesterol. We suggest that complement activation is associated with the various lipid disorders and is more important in those dyslipidemic conditions in which other factors may be involved. In particular, hypertriglyceridemia may be associated with endothelial and fibrinolytic disturbances, and the decrease of HDL may induce the failure of the regulatory proteins transported by the same HDL.

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 ± 9.9% in FH patients and 9.1 ± 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 ± 9.1% in the third month and to 21.2 ± 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.

Apolipoprotein E polymorphism and the distribution profile of very low density lipoproteins; an influence of the E4 allele on large (Sf>60) particles

Very low density lipoprotein (VLDL) distribution and composition have been examined as a function of apo E genotype (E2/2+E2/3 vs. E3/3 vs. E3/4+E4/4) in healthy, normolipaemic subjects. Apo E genotype had a marked impact on plasma concentrations of apo E rich VLDL, but no influence on concentrations of apo E free particles. Thus, there was a trend to lower concentrations of apo E rich total VLDL in apo E4 carriers (mg/dl; E2, 49.1±35.2; E3, 52.5±30.9; E4 35.2±22.3; ANOVA P=0.16; when comparing E4 with E2+E3, P=0.06). Consequently, there were highly significant differences between apo E-defined subgroups in terms of the percentage distribution of bound and non-bound fractions (% total VLDL non-bound to apo E: E2, 44.0±12.7%; E3, 39.7±8.7%; E4 51.0±12.2%; ANOVA P=0.007). Subfractionation of VLDL into density subclasses revealed that genotype differences were restricted to large VLDL (Sf>60). Significantly lower concentrations of apo E-rich particles were observed in E4 carriers for VLDL-1 Sf 400–100 (ANOVA P=0.004) and VLDL-2 ( P=0.009) but not for small VLDL-3 Sf 60–20 ( P=0.34). No differences in plasma concentrations of apo E free VLDL were observed between genotype subclasses across the density spectrum. Compositional differences between the apo E defined VLDL were also evident for the core lipids. Apo E containing VLDL was enriched in esterified cholesterol and depleted in triglycerides compared to apo E poor VLDL: the difference became more marked with increasing density of the particles. Lipoprotein composition was not modulated to any great extent by apo E genotype. In patients with familial hypercholesterolaemia, relative concentrations of apo E rich, large VLDL were significantly higher than in controls. Treatment lowered concentrations of both apo E rich and apo E free VLDL but led to a greater relative enrichment of large VLDL in apo E containing particles. Apo E polymorphism appears to influence plasma concentrations of VLDL particles. The data are consistent with more pronounced receptor-mediated elimination of apo E4 containing VLDL. This may be a contributory factor to the down regulation of receptor activity which is suggested to be of major importance in provoking higher cholesterol levels associated with the apo E4 isoform.

4.P.202 Reduced plasma capacity of cholesterol efflux, delayed postprandial lipid response, and abnormal Apo-CIII distribution in normolipemic subjects with premature coronary heart disease

4.P.202 Reduced plasma capacity of cholesterol efflux, delayed postprandial lipid response, and abnormal Apo-CIII distribution in normolipemic subjects with premature coronary heart disease

Relations Between Plasma Lipids and Postheparin Plasma Lipases and VLDL and LDL Subfraction Patterns in Normolipemic Men and Women

VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)

Lipoprotein(a): Levels in a Swedish population in relation to other lipid parameters and in comparison with a male Sri Lankan population

Objective: To evaluate differences in Lipoprotein (a) [Lp(a)] concentrations between a Swedish and Sri Lankan population. Methods: The distribution of L.p(a) and its relation to other lipid parameters, measured with an automated turbidimetric method, in 4646 Swedes (1944 females and 2702 males) undergoing health screening and 757 randomly selected Sri Lankan males (667 non-CHD and 80 CHD subjects) was evaluated. Results: The distribution was highly skewed towards low values in both the Swedish population and the Sri Lankan male population. The Swedish population had a median of 0.16 g/L (reported as total mass) whereas the Sri Lankan population median of 0.06 g/L was much lower. For the Swedes, there was a small significant difference of 0.03 g/L between the sexes (F < M; p < 0.001) and Lp(a) was significantly higher in subjects >50 years of age in both sexes ( p < 0.002(F); p < 0.02(M)). 29% had Lp(a) values >0.30 g/L. In the Sri Lankan males population Lp(a) was also significantly higher in subjects >50 years of age ( p < 0.009) but only 7% had an Lp(a) concentration of >0.30 g/L. In the CHD subgroup, though not significant, subjects >50 years of age had a lower Lp(a) concentration, indicating that Lp(a) may be a more significant risk factor in younger subjects. Both the Swedish female and male hypercholesterolemic subgroups had significantly higher Lp(a) concentrations than normolipemic subgroups and the male hypertriglyceridemic subgroups significantly lower Lp(a) concentrations than normolipemic. Great differences in Lp(a) levels are thus found between the two populations. The differences are similar in normolipemic subjects and probably they reflect mainly genetic differences. Lipid/ lipoprotein concentrations were also found to differ. It is being investigated if this reflects differences in CHD prevalence. Conclusion: Our data support the importance of including Lp(a) measurements when assessing the risk profile for premature development of CHD in the individual patient.

Lipid Transfer Inhibitor Activity (LTIA) present in plasma high-density lipoproteins of normolipemic subjects is not correlated with Lipid Transfer Activity (LTA)

Lipid Transfer Inhibitor Activity (LTIA) present in plasma high-density lipoproteins of normolipemic subjects is not correlated with Lipid Transfer Activity (LTA)

Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men.

To further understand the factors involved in the regulation of high plasma triglyceride (TG) or low plasma high density lipoprotein cholesterol (HDL-C) levels, three groups of male subjects (normal TG with low HDL-C levels, high TG with normal HDL-C levels, and high TG with low HDL-C levels) were compared with a sample of normolipemic men with normal TG and HDL-C plasma levels. Mean age was 34 years (range, 20-42 years), and none of the subjects had plasma TG levels > 4.0 mmol/l or familial hypercholesterolemia. Both groups of subjects with high TG levels had a higher body mass index, waist circumference, waist-to-hip circumferences ratio, and a higher ratio of abdominal to femoral adipose tissue areas as measured by computed tomography when compared with normolipemic control subjects. However, during an oral glucose tolerance test only high TG-low HDL-C men had fasting hyperinsulinemia and higher plasma insulin levels compared with normolipemic subjects. In addition, the high TG-low HDL-C group showed reduced HDL apoprotein (apo) A-I levels and a low HDL2-C/HDL3-C ratio. These changes were observed along with a nonsignificant trend for a lower plasma postheparin lipoprotein lipase activity. However, among subjects with high TG and normal HDL-C levels, no evidence of insulin resistance or of a reduction in postheparin lipoprotein lipase activity was observed, suggesting that the high plasma TG levels could be attributed to an increased production of apo B-containing lipoproteins, as high plasma apo B and low density lipoprotein (LDL)-apo B levels were observed in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-Containing Lipoprotein Particles: Physiological Role, Quantification, and Clinical Significance

High-density lipoprotein (HDL) particles are made up of two major populations of particles, differing in composition and metabolism. Both contain apolipoprotein (apo) A-I but only one contains apo A-II. Lipoprotein particles that contain only apo A-I (LpA-I particles) can increase cellular cholesterol efflux from cultured cells in vitro. LpA-I:A-II particles, however, do not increase cholesterol efflux. LpA-I:A-II can be determined directly with an enzyme-linked differential antibody immunosorbent assay. LpA-I is determined by differential electroimmunoassay: in the presence of a large excess of anti-apo A-II, LpA-I:A-II particles are retained in one peak, whereas LpA-I migrates grates as a second peak. Both lipoprotein forms of apo A-I-containing particles are present mainly in HDL, but the relative proportion of LpA-I is greater in HDL2 than in HDL3. Concentrations of LpA-I in plasma samples from normolipemic subjects average approximately 10% higher in women than in men. The lower apo A-I concentrations in patients with significant coronary artery disease reflect a decrease in the LpA-I particles. Data obtained in octogenarians also support the possibility that LpA-I might represent the anti-atherogenic fraction of HDL. Moreover, the concentration of LpA-I in children of parents with premature coronary heart disease was lower than that of a control group without any family history of this disease. Nutrients and hypolipidemic drugs seem to affect the two kinds of particles differently.

Concentrations of high-density lipoprotein subfraction HDL2 and lipoprotein A-I in a random population of healthy subjects

High-density lipoproteins (HDL) are now currently subdivided according either to density and size-HDL2 and HDL3--or to surface apoprotein composition--lipoprotein A-I (LpA-I) without A-II, and LpA-I:A-II. In samples from blood bank donors (60 women, 47 men), we evaluated HDL subclasses, LpA-I particles, and other classic risk factors for atherosclerosis and compared them with each other. We found a good correlation between HDL2 and LpA-I (r = 0.74, P less than 0.001), the correlation being more marked in women (r = 0.74) than in men (r = 0.67). LpA-I was also strongly correlated with total apolipoprotein A-I (apoA-I) (r = 0.61), which suggests that LpA-I represents a significant portion of the variable pool of apoA-I. By contrast, LpA-I:A-II but not LpA-I was correlated with HDL3, confirming the preferential association of LpA-I with HDL2. The difference between the sexes was more marked for HDL2 (+66% in women) than for LpA-I (+25%). We conclude that in normolipemic subjects the size of the HDL2 pool depends on that of LpA-I. Considering the speed and low cost of the assay, determination of HDL2 cholesterol might be a useful tool for assessing cardiovascular risk.

Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects.

This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL). Subjects homozygous for E3 converted approximately 50% of LVDL2 to LDL, the remainder being lost by direct catabolism. Those with the E2 phenotype produced less VLDL1, but converted more of it to VLDL2 (compared to E3 subjects). They displayed a characteristic dyslipidemia with the presence of slowly catabolized VLDL1 and VLDL2 remnants. LDL levels were low owing to increased direct catabolism of VLDL2 and IDL and a reduced efficiency of delipidation; only 25% of VLDL2 apo B was directed to LDL production. In contrast, E4 subjects converted more VLDL2 apo B to LDL than E3 subjects. About 70% of VLDL2 apo B was found in LDL; direct catabolism of VLDL and IDL was reduced as was the fractional catabolic rate of LDL (0.2 vs. 0.26 in E3 subjects). These changes in the VLDL----IDL----LDL metabolic cascade can in part be explained by alterations in hepatic LDL receptors with E2 subjects having higher and E4 subjects lower activities than those in E3 homozygotes.

Effects of dietary fish oil supplementation on platelet aggregability and platelet membrane fluidity in normolipemic subjects with and without high plasma Lp(a) concentrations

The purpose of this study was to compare the relative effect of n − 3 fatty acids on plasma lipids and platelet function in normolipemic subjects n − 8 with plasma Lp(a) levels > 30 mg/dl and normolipemic subjects n − 7 without detectable plasma Lp(a) concentrations. Six weeks of dietary supplementation (3.8 g EPA and 2.9 g DHA/d) significantly reduced ( P < 0.005) plasma TGs in both groups whereas no changes of plasma TC, LDL-C, HDL-C, and Lp(a), respectively, were found. Collagen- or thrombin-stimulated platelet aggregation and collagen- or thrombin-induced TXB 2 generation from platelets decreased by approx. 45% in Lp(a)-negative and Lp(a)-positive platelet donors after a 6 week dietary intake. Four more weeks without n − 3 supplementation restored the pretreatment values of TGs, platelet aggregability and TXB 2 release. The biophysical properties of platelets from normolipemics with and without high plasma Lp(a) concentrations revealed a similar structural order of platelets at 37°C using DPH, TMA-DPH, or 6-AS as fluorescent probes. Also similar temperature-dependent changes in platelet fluidity from 37°C to 17°C were observed in platelet preparations from Lp(a)-positive and Lp(a)-negative subjects. However, no subtle changes in the structural order of platelets due to nutrient intakes were found in all subjects ( n = 15, 19–28 yrs) using fluorescence polarization technique. The present data suggest a similar in vitro platelet behaviour from normolipemic subjects with and without high plasma levels of Lp(a) (which is considered a risk for premature atherosclerosis) in contrast to platelet aggregability and platelet fluidity in certain hyperlipidemic stages.

Absorption of the n − 3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans

Five normolipemic subjects received three test meals containing 28 g n-3 (omega-3) fatty acids provided as 1) triglycerides, 2) ethyl esters, and 3) ethyl esters + 12 g olive oil. The control meal contained olive oil. When equivalent amounts of fat were given, the increase in chylomicron and plasma triglycerides was similar; n-3 fatty acid contents were also similar after n-3 fatty acid intake as ethyl esters or triglycerides. Ethyl esters alone were well absorbed and produced similar n-3 fatty acid responses in plasma triglycerides and chylomicrons. At 24 h after the n-3 fatty acid-containing meals, the fatty acid plasma concentration of these acids was similar. This study showed that n-3 fatty acids in fish oil given as ethyl esters or triglycerides were equally well absorbed. Eicosapentaenoic and docosahexaenoic acids were also equally absorbed.