Postprandial plasma lipoprotein changes in human subjects of different ages

Plasma lipoprotein changes were monitored for 12 hr after a fat-rich meal (1 g of fat/kg body weight) in 22 subjects (9 males, 13 females, 22-79 yr old). Plasma triglyceride, measured hourly, peaked once in some subjects, but twice or three times in others. The magnitude of postprandial triglyceridemia varied considerably between subjects (range: 650-4082 mg.hr/dl). Males tended to have greater postprandial triglyceridemia than females, and elderly subjects had significantly (P less than 0.05) greater postprandial triglyceridemia than younger subjects. Total plasma cholesterol, measured every three hr, increased significantly (6.0 +/- 2.1%) in 7 subjects, decreased significantly (7.1 +/- 1.2%) in 10 subjects, and remained unchanged in the remainder. Single spin ultracentrifugation and dextran sulfate precipitation procedures were used to quantitate triglyceride and cholesterol in triglyceride-rich lipoproteins (TRL, d less than 1.006 g/ml), low density lipoproteins (LDL), and high density lipoproteins (HDL). Plasma TRL and HDL triglyceride increased after the fat meal, while LDL triglyceride decreased at 3 hr but increased at 9 and 12 hr. TRL cholesterol increased postprandially, while LDL and HDL cholesterol decreased. Phospholipid (PL), free (FC) and esterified (EC) cholesterol measurements were carried out on the plasma and lipoprotein fractions of 8 subjects. Plasma PL increased significantly at 3, 6, and 9 hr after the fat-rich meal, due to increases in TRL and HDL PL. TRL CE increased postprandially, but a greater decrease in LDL and HDL CE caused plasma CE to be decreased. Plasma FC increased, predominantly due to an increase in TRL FC. Plasma concentrations of apolipoprotein A-I and apolipoprotein B both decreased after the fat-rich meal. The magnitude of postprandial triglyceridemia was inversely correlated with HDL cholesterol levels (r = -0.502, P less than 0.05) and positively correlated with age (r = -0.449, P less than 0.05), fasting levels of plasma triglyceride (r = 0.636, P less than 0.01), plasma apoB (r = 0.510, P less than 0.05), TRL triglyceride (r = 0.564, P less than 0.01), TRL cholesterol (r = 0.480, P less than 0.05) and LDL triglyceride (r = 0.566, P less than 0.01). Change in postprandial cholesterolemia was inversely correlated with fasting levels of HDL cholesterol (r = -0.451, P less than 0.05) and plasma apoA-I (r = -0.436, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test

Elevated plasma concentration of chylomicron remnants may be causally related to atherosclerosis in obesity. We examined the effect of atorvastatin on chylomicron remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion labeled with cholesteryl [(13)C]oleate was injected intravenously into patients; the fractional catabolic rate (FCR) of the remnant-like emulsion was determined by measurement of (13)CO(2) in the breath and analyzed using compartmental modelling. Compared with placebo, atorvastatin significantly decreased the plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B (apoB), and lathosterol (P < 0.001). ApoB-48 and remnant-like particle-cholesterol (RLP-C) both decreased significantly by 23% (P = 0.002) and 33% (P = 0.045), respectively. The FCR of the remnant-like emulsion increased significantly from 0.054 +/- 0.008 to 0.090 +/- 0.010 pools/h (P = 0.002). The decrease in RLP-C was associated with the decrease in plasma triglycerides (r = 0.750, P = 0.003). Furthermore, the change in FCR of remnant-like emulsions was inversely associated with the change in LDL-C (r = -0.575, P = 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor pathways. We conclude that in obese subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride-rich remnants and that this may be partially due to an enhancement in hepatic clearance of these lipoproteins.     

Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal

Twenty two subjects (9 males, 13 females) were fed a fat-rich meal (1 g of fat/kg body weight). Triglyceride-rich lipoproteins (TRL) were isolated by ultracentrifugation (d less than 1.006 g/ml) from blood drawn 0, 3, 6, 9, and 12 hr after the meal. Plasma triglyceride increased then decreased postprandially, while plasma apoA-I and apoB concentrations decreased. TRL triglyceride, TRL total protein, and TRL apoB concentrations all increased then decreased after the fat-rich meal. Postprandial rise in plasma triglyceride was significantly correlated with fasting plasma triglyceride levels (r = 0.66, P less than 0.001); postprandial rise in TRL triglyceride was significantly correlated with fasting TRL triglyceride levels (r = 0.58, P less than 0.01); postprandial rise in TRL apoB was not, however, significantly correlated with fasting TRL apoB levels (r = 0.37, N.S.). TRL apolipoproteins were separated by polyacrylamide gradient (4-22.5%) gel electrophoresis and protein bands were scanned in two dimensions with a laser densitometer. Relative postprandial changes in the concentration of the TRL apolipoproteins were determined. TRL apoB-100, apoB-48, apoE, and apoC increased then decreased postprandially. The increase in TRL apoB-100 after the fat-rich meal was confirmed in 8 subjects by direct measurement of apoB-100 with a monoclonal antibody ELISA assay. ApoA-I concentration in TRL was unchanged. Albumin in the TRL fraction was significantly increased 12 hr after the meal. Subjects with a greater magnitude of postprandial triglyceridemia had a greater increase in TRL triglyceride and TRL apoB, but their TRL apoB-100/apoB-48 ratios were not different from subjects with less pronounced triglyceridemia. Assuming that plasma TRL containing apoB-100 are predominantly derived from the liver, our data suggest that triglyceride-rich lipoproteins from both the liver and intestine make a significant contribution to postprandial triglyceridemia.     

Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state

Potentially atherogenic triglyceride-rich lipoprotein (TRL) remnants can be isolated and quantitated as remnant-like particles (RLP), using an immunoaffinity gel containing specific anti-human apolipoprotein A-I (apoA-I) and apoB-100 monoclonal antibodies. The aim of the present study was to determine the relationship between postprandial changes in RLP levels and changes in total serum triglyceride (TG) in patients with different forms of hypertriglyceridemia (HTG). Three groups of patients were selected, having similarly elevated serum TG levels: a) HTG with TRL remnant accumulation (i.e., type III patients, n = 15, TG: 3.8 +/- 0.2 mm), b) HTG with increased LDL (i.e., type IIb patients, n = 15, TG: 3.7 +/- 0.2 mm), and c) HTG without evidence of remnant or LDL accumulation (i.e., type IV patients, n = 15, TG: 3.9 +/- 0.3 mm). Ingestion of a 45-g fat meal caused a significant increase in serum TG (30;-50%) in all patients. Mean serum TG levels of the three groups were not significantly different at 4 or 6 h after the meal. RLP cholesterol (C) and TG levels increased after the meal in all patients, but these postprandial increases were also not significantly different among groups. Type III patients had significantly higher (P < 0.01) levels of RLP-C and RLP-apoE in the fasted and fed state, and also had significantly higher RLP-C-to-serum TG ratios (P < 0.001) compared with the other groups. These results indicate that 1) RLP-C and RLP-TG levels are significantly increased in the fed versus fasted state in patients with elevated fasting TG levels; 2) patients with different forms of HTG, but similar TG levels, have similar postprandial increases in RLP-C and RLP-TG; and 3) type III patients have significantly elevated levels of RLP-C and RLP-apoE in both the fed and fasted state.     

急性脑出血患者颈动脉斑块与血清hs CRP 及HbAlc的相关性研究

目的:探究急性脑出血患者颈动脉斑块与血清超敏C反应蛋白(hs-CRP)及糖化血红蛋白(Hb Alc)的相关性。方法:随机选取我院2013年5月至2015年1月脑科收治的急性脑出血患者84例,根据颈动脉粥样硬化标准将所有患者分为单纯脑出血组(n=25)、轻度粥样硬化组(n=34)和重度粥样硬化组(n=25)三组,另选取同期我院健康体检者50人(对照组)。对比分析四组颈总动脉膜厚度(IMT)空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、hs-CRP与Hb Alc水平,分析急性脑出血患者颈动脉斑块的危险因素。结果:四组的IMT、TC、TG、HDL、LDL、hs-CRP和Hb Alc水平差异均具有统计学意义(P0.05),其中hs-CRP和Hb Alc水平在单纯脑出血组轻度粥样硬化组重度粥样硬化组(P0.05);IMT与hs-CRP和Hb Alc均呈现正相关(r=0.388、0.420,P0.05);IMT、hs-CRP和Hb Alc均为颈动脉粥样硬化的危险因素(OR=3.065、1.978、1.647,P0.05)。结论:急性脑出血患者体内hs-CRP及Hb Alc水平是颈动脉斑块形成的危险因素。     

Postprandial low-density lipoproteins in type 2 diabetes are oxidized more extensively than fasting diabetes and control samples

This study examined the kinetics of low-density lipoprotein (LDL) oxidation in the fasting and postprandial states of diabetic and control subjects to determine if LDL oxidation may contribute to accelerated atherosclerosis in diabetes. We compared in vitro oxidation of LDL from 12 control and 13 Type 2 diabetic subjects in the fasting and postprandial states. The extent of oxidation was assessed by length of lag phase, formation of conjugated dienes (CD), lipid peroxides, thiobarbituric acid reactive substances (TBARS), and percentage reduction in free amine groups. Diabetic subjects were significantly older and heavier. Comparisons between control and diabetic subjects in the postprandial state showed that the lag phase was significantly shorter in diabetic subjects than controls (P = 0.005), TBARS were significantly higher (P = 0.006), and levels of CD were higher at 60, 65, and 70 min (P < 0.01). In the fasting state, however, these comparisons were not significant. In diabetic subjects, postprandial samples had a significantly shorter lag phase (P = 0.003), higher TBARS (P = 0.006), and higher levels of CD at 60, 65 (P < 0.001), and 70 min (P = 0.0013) compared to fasting samples. Elevated levels of serum triglycerides in diabetic subjects were negatively correlated to lag phase, in fasting (P = 0.06) and postprandial states (P = 0.002). We conclude that accelerated oxidation of LDL seen in postprandial states in diabetes may be a critical contributor to cardiovascular risks. Elevated levels of serum triglycerides may contribute to the rapid oxidation of LDL seen in diabetic subjects.     

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.     

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion of a stable isotope in the fed state. The coadministration of simvastatin and ezetimibe significantly reduced plasma concentrations of cholesterol (−43.0%), LDL-C (−53.6%), and triglycerides (−44.0%). Triglyceride-rich lipoproteins (TRL) apoB-48 pool size (PS) was significantly decreased (−48.9%) following combination therapy mainly through a significant reduction in TRL apoB-48 production rate (PR) (−38.0%). The fractional catabolic rate (FCR) of VLDL and LDL apoB-100 were significantly increased with all treatment modalities compared with placebo, leading to a significant reduction in the PS of these fractions. We also observed a positive correlation between changes in TRL apoB-48 PS and changes in TRL apoB-48 PR (r = 0.85; P < 0.0001) with combination therapy. Our results indicate that treatment with simvastatin plus ezetimibe is effective in reducing plasma TRL apoB-48 levels and that this effect is most likely mediated by a reduction in the intestinal secretion of TRL apoB-48. Our study also indicated that the reduction in LDL-C concentration following combination therapy is mainly driven by an increase in FCR of apoB-100 containing lipoproteins.     

Ezetimibe ameliorates intestinal chylomicron overproduction and improves glucose tolerance in a diet-induced hamster model of insulin resistance

Ezetimibe is a cholesterol uptake inhibitor that targets the Niemann-Pick C1-like 1 cholesterol transporter. Ezetimibe treatment has been shown to cause significant decreases in plasma cholesterol levels in patients with hypercholesterolemia and familial hypercholesterolemia. A recent study in humans has shown that ezetimibe can decrease the release of atherogenic postprandial intestinal lipoproteins. In the present study, we evaluated the mechanisms by which ezetimibe treatment can lower postprandial apoB48-containing chylomicron particles, using a hyperlipidemic and insulin-resistant hamster model fed a diet rich in fructose and fat (the FF diet) and fructose, fat, and cholesterol (the FFC diet). Male Syrian Golden hamsters were fed either chow or the FF or FFC diet ± ezetimibe for 2 wk. After 2 wk, chylomicron production was assessed following intravenous triton infusion. Tissues were then collected and analyzed for protein and mRNA content. FFC-fed hamsters treated with ezetimibe showed improved glucose tolerance, decreased fasting insulin levels, and markedly reduced circulating levels of TG and cholesterol in both the LDL and VLDL fractions. Examination of triglyceride (TG)-rich lipoprotein (TRL) fractions showed that ezetimibe treatment reduced postprandial cholesterol content in TRL lipoproteins as well as reducing apoB48 content. Although ezetimibe did not decrease TRL-TG levels in FFC hamsters, ezetimibe treatment in FF hamsters resulted in decreases in TRL-TG. Jejunal apoB48 protein expression was lower in ezetimibe-treated hamsters. Reductions in jejunal protein levels of scavenger receptor type B-1 (SRB-1) and fatty acid transport protein 4 were also observed. In addition, ezetimibe-treated hamsters showed significantly lower jejunal mRNA expression of a number of genes involved in lipid synthesis and transport, including srebp-1c, sr-b1, ppar-γ, and abcg1. These data suggest that treatment with ezetimibe not only inhibits cholesterol uptake, but may also alter intestinal function to promote improved handling of dietary lipids and reduced chylomicron production. These, in turn, promote decreases in fasting and postprandial lipid levels and improvements in glucose homeostasis.     

Carotenoids and asymptomatic carotid atherosclerosis

High plasma concentrations of lycopene and beta-carotene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of these carotenoids in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and sixty-five subjects underwent physical examination and ultrasonic measurement of common carotid artery intima-media thickness. Analysis of variance and logistic regression methods were used to determine whether differences existed between participants with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. Of the 165 participants, 80 exhibited evidence of carotid atherosclerosis (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness<0.8 mm). Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly greater body mass index, significantly higher serum concentrations of total cholesterol, LDL-associated cholesterol and triglycerides, and significantly higher plasma concentrations of uric acid, C-reactive protein and fibrinogen. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene and beta-carotene. These results suggest that lycopene and beta-carotene may play important roles in delaying the development of the early asymptomatic stage of carotid atherosclerosis. Encouraging adequate intakes of antioxidant carotenoids may provide an important public health service.     

Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide

The aim of this study was to test the hypothesis that autoantibodies recognize amino acid sequences in the LDL receptor binding region of apolipoprotein B-100 (apoB-100). Autoantibodies against an unmodified or malondialdehyde (MDA)-modified LDL receptor binding site peptide were determined by ELISA in baseline plasma samples of 78 cases with coronary events and 149 matched controls recruited from the prospective Malm? Diet Cancer Study. IgG and IgM recognizing this peptide were detected in all subjects but did not differ between cases and controls. Inverse associations were observed between IgG against the native binding site and plasma oxidized LDL (r = -0.21, P < 0.005), but there were no significant associations with total or LDL cholesterol levels. In univariate analyses, inverse associations were found between baseline carotid intima-media thickness and IgG against the MDA-modified binding site (r = -0.14, P < 0.05), but this association was lost when controlling for other major cardiovascular risk factors. Specificity studies demonstrated that the binding of autoantibodies to these sequences could be inhibited by oxidized but not by native LDL. Autoantibodies recognizing the LDL receptor binding site in apoB-100 are frequently expressed. Their association with plasma oxidized LDL suggests that they have been generated in response to breakdown products of LDL oxidation, but their influence on cholesterol metabolism and the development of atherosclerosis appears limited.     

LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins

Small, dense LDL particles are typical for FCHL. Intravascular lipid exchange and net transfer among HDL, LDL, and triglyceride-rich lipoproteins as well as lipolysis in the VLDL-IDL-LDL cascade regulate properties of LDL. We investigated postheparin plasma activities of hepatic lipase (HL) and LPL, and plasma activities of CETP and phospholipid transfer protein (PLTP) in 191 individuals from 37 Finnish FCHL families. LDL peak particle diameter (LDL size) was measured with 2-10% gradient polyacrylamide gel electrophoresis. LDL size was significantly smaller in affected FCHL family members (n = 68) as compared with nonaffected FCHL family members (n = 78) or spouses (n = 45) (25.3 +/- 1.5 nm, 26.8 +/- 1.2 nm, and 26.6 +/- 1.2 nm, respectively, P < 0.001 for both). In affected FCHL family members, serum triglycerides were the strongest correlate for LDL size (r = -0.71, P < 0.001). In univariate correlation analysis LDL size was not associated with HL, LPL, CETP, and PLTP activities. In multivariate stepwise regression analysis, however, serum triglycerides, CETP activity, HL activity, and HDL cholesterol were significant predictors of LDL size in affected FCHL subjects (adjusted r (2) = 0.642).We conclude that serum triglyceride concentration is strongly correlated with LDL size in affected FCHL subjects. After adjustment for serum triglycerides, HL and CETP activities are associated with LDL size in FCHL.     

Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors

The effects of daily supplemental chromium (200 μg) complexed with 1.8 mg nicotinic acid on plasma glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, were assessed in 14 healthy adults and 5 adults with noninsulin-dependent diabetes mellitus (NIDDM) using a double-blind crossover study with 8-wk experimental periods. Eight of the 14 healthy subjects and all 5 subjects with NIDDM also underwent an oral glucose tolerance test with assessment of 90 min postprandial plasma glucose and insulin concentrations. No statistically significant effects of chromium nicotinic acid supplementation were found on plasma insulin, glucose, or lipid concentrations, although chromium nicotinic acid supplementation slightly lowered fasting plasma total and LDL cholesterol, triglycerides, and glucose concentrations, and 90-min postprandial glucose concentrations in individuals with NIDDM.     

Metabolism of human plasma triacylglycerol-rich lipoproteins in rodent macrophages: capacity for interaction at beta-VLDL receptor

The capacity of human plasma triacylglycerol-rich lipoproteins to be metabolized by rat macrophages was studied with plasma triacylglycerol-rich lipoproteins obtained from subjects with fasting chylomicronemia or from normal subjects after a fat meal. Triacylglycerol-rich lipoproteins were separated by chromatography into two fractions designated TRL1 and TRL2; from their composition and changing concentration during alimentary lipemia, TRL1 contained a higher proportion of chylomicron remnants than TRL2. Degradation of 125I-labeled TRL1 was greater than that of 125I-labeled TRL2. In competition studies with 125I-labeled beta-VLDL from cholesterol-fed rabbits, unlabeled TRL1 displaced beta-VLDL as completely as did unlabeled beta-VLDL, being slightly more potent than TRL2, which contained less apolipoprotein E than TRL1. This reflected common interaction at receptors that probably included both beta-VLDL and B/E receptors, since: (1) in fresh macrophages, VLDL from hypertriglyceridemic subjects partially displaced beta-VLDL; (2) in B/E receptor-repressed macrophages, TRL1 maintained capacity to totally displace beta-VLDL. This was confirmed in experiments with J774 murine macrophages in which triacylglycerol-rich lipoproteins and beta-VLDL displaced each other equally, whereas LDL was ineffective in displacing beta-VLDL. Furthermore, monoclonal antibodies raised against apolipoprotein B48 and reacting strongly with LDL, failed to inhibit the binding of triacylglycerol-rich lipoprotein to the macrophages. This indicates an interaction through apolipoprotein E which is present in high concentration in triacylglycerol-rich lipoprotein as well as in beta-VLDL. It applies to triacylglycerol-rich particles derived from either the intestine (chylomicron remnants) or the liver (VLDL remnants from hypertriglyceridemic subjects).     

Oxidized LDL autoantibodies are related to apolipoprotein E phenotype,independently of postprandial change in plasma triglycerides and LDL size,among patients with angiographically verified coronary artery disease and healthy controls

OBJECTIVE: Oxidized low-density lipoprotein (LDL) autoantibodies (oxLDLab), apolipoprotein E (apoE) phenotype, postprandial triglyceride changes and LDL size are suggested to be risk factors for coronary artery disease (CAD). Our aim was to study the interaction between these new risk factors among patients with CAD and healthy controls. METHODS: oxLDLab from 31 men with angiographically verified CAD and 31 healthy men were analyzed by enzyme-linked immunosorbent assay. Isoelectric focusing and immunoblotting were used for apoE phenotyping. Triglyceride level was measured after 12 h of fasting and 3, 5 and 7 h after a high-fat meal. Nondenaturing gradient gel electrophoresis was used to separate LDL particles according to size. RESULTS: oxLD- Lab levels increased according to apoE phenotype in the following order: E2 < E3 < E4 (p = 0.004, ANOVA). The postprandial response of triglycerides, the size of LDL particles and the concentration of LDL and high-density lipoprotein (HDL) cholesterol did not differ between apoE phenotypes, and the use of these variables as covariates did not change the statistically significant difference in oxLDLab levels between apoE phenotypes (p = 0.01, ANCOVA). oxLDLab levels did not differ between the patient and control groups. CONCLUSION: We found an association between apoE allele epsilon2 and decreased levels of oxLDLab, which was independent of the postprandial response of triglycerides, the size of LDL particles and plasma LDL and HDL cholesterol levels. The mechanism by which apoE affects oxidation of LDL remains unknown.     

Characterization of a more electronegatively charged LDL subfraction by ion exchange HPLC

Low density lipoproteins (LDL), collected from 32 normal male subjects (aged 30-60), were subfractionated by high resolution ion exchange chromatography (IE-HPLC). By this procedure two LDL subfractions were eluted. The first corresponds to normal LDL (nLDL); while the second one corresponds to a more electronegative subfraction, called LDL-. The mean percentage contribution of LDL- to native plasma LDL was of 3.9% (range 0.5-9.8%). The percentage concentration of LDL- in total native LDL did not correlate with plasma total cholesterol, triglycerides, and LDL cholesterol, whereas a significant negative correlation with high density lipoprotein cholesterol was found (r = -.38; p less than .05). LDL- was negatively correlated with LDL phospholipids (r = -.59; p less than .001), and with the LDL vitamin E content (r = -.63; p less than .001), and positively correlated with LDL proteins (r = -.35; p less than .05) and the content of thiobarbituric acid reactive substances (TBARS) in total LDL (r = .43; p less than .05). The TBARS molar content of LDL- was three times higher than in nLDL, with a mean concentration in LDL- of 7.3 mol/mol lipoprotein. By preparative IE-HPLC significant differences of the LDL- chemical composition were observed. The percentage content of cholesterol esters and of phospholipids was decreased, whereas proteins and free cholesterol were increased. Analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis revealed that besides apolipoprotein B-100 there was evidence of peptides with a higher molecular weight in LDL-.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP

We examined whether postprandial (PP) chylomicrons (CMs) can serve as vehicles for transporting cholesterol from endogenous cholesterol-rich lipoprotein (LDL+HDL) fractions and cell membranes to the liver via lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. During incubation of fresh fasting and PP plasma containing [(3)H]cholesteryl ester (CE)-labeled LDL+HDL, both CMs and VLDL served as acceptors of [(3)H]CE or cholesterol from LDL+HDL. The presence of CMs in PP plasma suppressed the ability of VLDL to accept [(3)H]CE from LDL+HDL. In reconstituted plasma containing an equivalent amount of triglycerides from isolated VLDL or CMs, a CM particle was about 40 times more potent than a VLDL particle in accepting [(3)H]CE or cholesterol from LDL+HDLs. When incubated with red blood cells (RBCs) as a source for cell membrane cholesterol, the cholesterol content of CMs, VLDL, LDL, and HDL in PP plasma increased by 485%, 74%, 13%, and 30%, respectively, via LCAT and CETP activities. The presence of CMs in plasma suppressed the ability of endogenous lipoproteins to accept cholesterol from RBCs. Our data suggest that PP CMs may play an important role in promoting reverse cholesterol transport in vivo by serving as the preferred ultimate vehicle for transporting cholesterol released from cell membranes to the liver via LCAT and CETP.     

The apo E/apo CIII molar ratio affects removal of cholesterol ester from modified human lipoproteins injected into cebus monkeys

The removal of postprandial (PP) and postabsorptive (PA) human LDL and HDL cholesterol was examined in cebus monkeys (Cebus albifrons) following in vitro labelling of these lipoproteins by 3H-cholesterol in the presence or absence of DTNB. The removal of LDL cholesteryl ester was 3.5 and 2 times greater than that of HDL in male and female monkeys, respectively. Incubation with DTNB reduced cholesteryl ester removal by 45 and 52% for LDL and HDL, respectively. Cholesteryl ester from PA lipoproteins was removed 80% faster than that PP particles only when plasma was incubated without DTNB. Cholesterol removal from these lipoproteins was positively (r = 0.941) and significantly (P less than 0.001) correlated with the molar apo E/apo CIII ratio. The data suggest that density of lipoproteins was less important than their apoprotein composition in dictating their removal from circulation.     

Preheparin lipoprotein lipolytic activities: relationship to plasma lipoproteins and postheparin lipolytic activities.

To determine the putative metabolic relevance of preheparin versus postheparin lipoprotein lipases, the relationships of both pre- and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) to plasma triglycerides, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol were determined in 93 men. Relationships of preheparin lipases to their respective postheparin lipases were also examined. Although relationships between the preheparin lipases and plasma triglycerides and HDL cholesterol were not apparent, both preheparin LPL (rs = 0.306, P = 0.0036) and HTGL (rs = 0.348, P = 0.0008) correlated with LDL cholesterol, a relationship not seen with either postheparin lipase. Both postheparin LPL (rs = 0.515, P = 0.0001) and postheparin HTGL (rs = -0.228, P = 0.0028), however, correlated with HDL cholesterol. In addition, postheparin LPL was inversely correlated with postheparin HTGL (rs = -0.363, P = 0.0003), whereas the relationship between preheparin LPL and preheparin HTGL was positive (rs = 0.228, P = 0.0009). Overall, these data point to differences between pre- and postheparin lipases in their relationships to lipoproteins, and one to another. The relationships of LDL cholesterol to both preheparin LPL and HTGL suggest that displacement of active forms of both lipases from their endothelial binding sites may mark triglyceride-rich lipoproteins or their remnants for metabolic pathways that lead to LDL.     

Association of fasting and nonfasting serum triglycerides with cardiovascular disease and the role of remnant-like lipoproteins and small dense LDL

PURPOSE OF REVIEW: The magnitude of the contribution of serum triglycerides to cardiovascular disease risk and the mechanisms by which triglyceride-rich lipoproteins exert their effect on the vascular wall are largely unknown. Postprandial lipemia likewise has been linked to atherosclerosis, but large prospective studies assessing the magnitude of this association are also lacking. Hypertriglyceridemia is characterized by the presence of cholesterol-rich remnant-like lipoproteins and small dense LDL particles, both of which are believed to contribute to cardiovascular disease risk. RECENT FINDINGS: Several large prospective cohort studies and a meta-analysis have been published recently, investigating the association of fasting and nonfasting serum triglycerides with cardiovascular disease. Fasting triglycerides increase the adjusted hazard ratios for cardiovascular disease risk 1.7 x (comparing upper with lower tertile), and nonfasting levels around 2.0 x. Measurement of nonfasting triglycerides may be more feasible and more informative, but standardization of a test meal is necessary. For clinical practice, the concentration of the atherogenic lipoprotein subfractions in hypertriglyceridemia may be reflected best by measuring apolipoprotein B. SUMMARY: Nonfasting triglyceride levels may replace fasting levels in assessing cardiovascular disease risk once standard reference values have been developed. Several atherogenic lipoprotein subfractions can be measured by including apolipoprotein B in addition to HDL, (nonfasting) triglycerides and LDL cholesterol.