Changes in Plasma LDL and HDL Composition in Patients Undergoing Cardiac Surgery

Changes of lipoprotein composition have been mainly reported in conditions of sepsis. This study characterized compositional changes in LDL and HDL during the acute phase response following cardiac surgery with cardiopulmonary bypass. Twenty-one patients undergoing cardiac surgery were included in this study. Blood samples were drawn before operation and on day 2 post-surgery. In parallel to plasma lipids and antioxidant status, lipoproteins were analyzed for lipid, apolipoprotein (apo), hydroperoxide and alpha-tocopherol content. Beyond decreases in lipid concentrations and antioxidant defenses, cardiac surgery induced substantial modifications in plasma lipoproteins. ApoB decrease in LDL fraction (−46%; P < 0.0001) reflected a marked reduction in the circulating particle number. LDL cholesteryl ester content relative to apoB concentration remained unchanged post-surgery while triglyceride (+113%; P < 0.001), free cholesterol (+22%; P < 0.05) and phospholipid (+23%; P < 0.025) were raised relative to apoB indicating increased particle size. In HDL, an abrupt rise of apoSAA (P < 0.05) was observed together with a decrease of apoA1 (−22%; P < 0.005). Cholesteryl ester content in HDL fraction decreased in parallel to apoA1 concentration while triglycerides, free cholesterol and phospholipids increased relative to apoA1. In contrast to unchanged alpha-tocopherol content, hydroperoxide content was increased in LDL and HDL. By comparison to sepsis, cardiac surgery induces a comparable reduction in circulating LDL but a more limited decrease in HDL particles. Furthermore, in contrast, cardiac surgery induces an increase in polar and non-polar lipids, as well as of particle size in both LDL and HDL. M. Hacquebard is recipient of a fellowship from the Danone Institute, Belgium.     

Differential Effects of Estrogen and Progestin on Apolipoprotein B100 and B48 Kinetics in Postmenopausal Women

The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B‐containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo‐controlled, randomized, double‐blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4‐week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride‐rich lipoproteins (TRL), intermediate‐density lipoproteins (IDL) and low ‐density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100‐ and apo B48‐containing lipoproteins.     

Xanthophylls, Phytosterols and Pre-β1-HDL are Differentially Affected by Fenofibrate and Niacin HDL-Raising in a Cross-Over Study

Fenofibrate and extended‐release (ER) niacin similarly raise high‐density lipoprotein cholesterol (HDL‐C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre‐β1‐HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER‐niacin (0.5 g/day for 3 week, then 1 g/day) in a cross‐over study. Both treatments increased HDL‐C (16 %) and apolipoprotein (apo) A‐I (7 %) but only fenofibrate increased apoA‐II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low‐density lipoprotein cholesterol and positively correlated with end of treatment apoA‐II. ApoA‐II in isolated HDL in vitro bound more lutein than apoA‐I. Xanthophylls were increased by ER‐niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre‐β1‐HDL was significantly decreased by fenofibrate (?19 %, p < 0.0001), with little change (3.4 %) for ER‐niacin. Although fenofibrate and ER‐niacin similarly increased plasma HDL‐C and apoA‐I, effects on plasma xanthophylls, phytosterols and pre‐β1‐HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA‐II in xanthophyll metabolism.     

Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A‐I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with ³H‐cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA‐I KO than in WT. In apoA‐I transgenic mice, LDE clearance was lower than in apoA‐I KO and than in apoA‐I KO infusion with human HDL. Infusion of human HDL into the apoA‐I KO mice resulted in higher LDE clearance than in the apoA‐I transgenic mice (p < 0.05). In apoA‐I KO and apoA‐I KO infused human HDL, the liver uptake was greater than in WT animals and apoA‐I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A‐I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA‐I also influences those processes.     

Differences in lipid parameters among statins treated patients with coronary arteriosclerosis – a pilot study

LDL, total cholesterol (TC), high‐density lipoprotein (HDL) are poor predictors of the cardiovascular risk among patients undergoing hypolipidaemic therapy with statins. Thus, in this pilot study we have attempted to determine, on the basis of routinely used assessments of lipid profiles, sensitive and inexpensive parameter which would associate with the severity of coronary artery disease in patients undergoing hypolipidaemic treatment who achieved LDL goal. Apolipoprotein (apo) B100, apoA1, LDL, triglycerides, HDL, lipoprotein (a) and TC levels were assessed in 140 patients referred for coronary angiography. The various ratios based on lipid parameters were calculated and compared to patients taking statins. Coronary arteriosclerosis was determined by the degree of single stenosis and quantitatively by applying the Gensini score. Uing multivariate analysis we have found that in the group with hypolipidaemic therapy and/or with treatment LDL target (70–100 mg/dL) the TC/apoB100 ratio was associated with coronary artery stenosis. Additionally, univariate analysis showed that the TC/apoB100 ratio (among treated subjects) was significantly lower in patients with haemodynamically significant stenosis of coronary arteries than in matched patients without coronary artery lesions.     

Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects

The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = −0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = −0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.     

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n=6) elevated serum triglycerides (+92% vs. baseline, P<.05), total cholesterol (+25% vs. baseline, P<.01), LDL cholesterol (+72% vs. baseline, P<.01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P<.01) and LDL cholesterol (+86% vs. baseline, P<.01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n=6). Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0–50%, n=6). In vitro, the addition of a fixed concentration of LEH (50%, n=6) to varying concentrations of cholesterol solution (0–50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.     

Association of L‐FABP T94A and MTP I128T Polymorphisms with Hyperlipidemia in Chinese Subjects

The purpose of this study was to evaluate the relation between the L‐FABP T94A and MTP I128T polymorphisms and hyperlipidemia in Chinese subjects. We recruited 390 volunteers: 201 hyperlipidemic and 189 healthy volunteers. The L‐FABP T94A and MTP I128T polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Anthropometry, lipid profile, and liver function of the subjects were determined. We observed that male carriers of the L‐FABP A94 allele had significantly higher body weight (P = 0.012), higher body mass index (BMI) (P = 0.014), and higher plasma triacylglycerol levels (TAG) (P = 0.033) and lower ratios of high‐density lipoprotein cholesterol (HDL‐C) to total cholesterol (TC) (P = 0.008) than T94 homozygotes. The MTP T128 allele was associated with significantly lower serum TC (P < 0.001) and low‐density lipoprotein cholesterol (LDL‐C) (P < 0.001) levels in males. There was a direct correlation between the MTP T128 allele and a decreased risk of hyperlipidemia after adjusting for body mass index (OR = 0.327, 95 % CI: 0.178–0.600, P < 0.001). In conclusion, both the MTP I128T and the L‐FABP T94A polymorphisms can affect serum lipid levels in the Chinese population. The MTP T128 allele offers protection against hyperlipidemia in the Chinese population.     

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.     

Endothelial vasodilatory function is predicted by circulating apolipoprotein B and HDL in healthy humans

Endothelium-dependent vasodilation (EDV), LDL particle size, and antibodies against oxidized LDL (oxLDLab) have been shown to be related to the development of atherosclerosis and cardiovascular disease. In this study, we investigated whether LDL particle size, oxLDLab, apolipoproteins, and lipoproteins are related to endothelial vasodilatory function in a population sample of 58 apparently healthy subjects aged 20 to 69 yr. EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm during local administration of methacholine chloride (2 and 4 μg/min) or sodium nitroprusside (5 and 10 μg/min). Forearm blood flow was determined with venous occlusion plethysmography. In multiple stepwise regression analyses, neither oxLDLab nor small LDL particles were significantly predictive of endothelial vasodilatory function. Instead, a high level of apolipoprotein B (apoB) was an independent predictor of both attenuated EDV and EIDV (r=−0.43, P<0.01, and r=−0.34, P<0.05, respectively). HDL cholesterol, on the other hand, was the only lipid variable that was significantly related to the EDV to EIDV ratio, an index of endothelial vasodilatory function (r=0.35, P<0.01). The inverse associations between apoB and both EDV and EIDV indicate that apoB might be an early marker of structural vascular changes in healthy subjects, whereas HDL seems to be more specifically related to endothelial vasodilatory function.     

A micro‐method for lipoprotein cholesterol profiles: Impact of CETP in KKAy mice

The aim of the present study was to assess cholesterol‐containing lipoprotein profiles in minute serum samples. The lipoprotein profiles of KKA^y and transgenic KKA^y‐CETP mice and of other species were determined. The transgenic KKA^y‐CETP mice express the simian enzyme cholesteryl ester transfer protein (CETP). The serum profile of the cholesterol‐containing high‐density (HDL), low‐density (LDL) and very‐low‐density lipoproteins (VLDL) was monitored on a Superose 6 column using fast protein liquid chromatography. Serum from several mouse and rat strains, rabbit, hamster, pig and man was included for comparative and method validation purposes. The chromatograms showed that the transgenic KKA^y‐CETP mice had significantly decreased relative levels of HDL vs. VLDL and LDL cholesterol (p <0.001). Introduction of the CETP gene shifted the serum profile of the cholesterol‐containing lipoproteins of the KKA^y‐CETP mice closer to the human profile in a dose‐dependent manner, thus making these mice an interesting model for man. The described lipoprotein separation technology offers promising and reliable opportunities for studies of blood lipoprotein profiles with minute serum samples, in both animals and man.     

Association of total cholesterol/apoB100 with lipid and protein oxidation products in stable angina patients treated with statins

Oxidative modification of lipids contained in lipoproteins may contribute to initiation of local inflammation in the vascular endothelium and ultimately to the atherosclerotic plaque formation. Therefore, in patients with high cardiovascular risk in primary as well as in secondary prevention, it is recommended that the serum low‐density lipoprotein (LDL) cholesterol be reduced. However, the management of patients with LDL level at goal is still a matter of debate. Various parameters have been proposed for predicting increased cardiovascular risk. It was found that among known indicators of lipid metabolism deregulation the ratio of total cholesterol/apoB100 associates with the severity of coronary arteriosclerosis in population of individuals with LDL levels < 100 mg/dL. There are several possible hypotheses for this phenomenon (impaired reduction of apoB100 expression by statins or increased triglyceride content of apoB100 containing lipoproteins compatible with oxidized LDL phenotype in subjects with high cardiovascular burden). In this paper, we discuss the increased susceptibility of plasma lipoproteins to oxidation. To verify this hypothesis, we undertook to determine, in the susceptible population described previously, whether there is a relation of total cholesterol (TC) ratio to apoB100 with known oxidative stress exponents such as protein and lipid oxidation products (LPP). TC/apoB100 was found to have a significant association with the level of LPPs in most examined subgroups (except subjects on statins with LDL > 100 mg/dL). See commentary by Grabowski http://dx.doi.org/10.1002/ejlt.201200295     

Do not use the Friedewald formula to calculate LDL‐cholesterol in hypercholesterolaemic rats

Reputable calculations such as the Friedewald formula are used extensively to determine LDL‐cholesterol (LDL‐C) values from known total cholesterol, triacylglycerol and HDL‐cholesterol (HDL‐C) levels. To the best of our knowledge, however, the validity of this equation has not yet been confirmed in rats. The aim of the present study is to give some insights as to why this formula must be used carefully in rats, and to find cut‐off points below which this formula can be considered reliable. Sera of 54 rats with different cholesterol, triacylglycerol and HDL‐C levels were tested. LDL was isolated by ultracentrifugation and LDL‐C measured by an enzymatic colorimetric method and compared against LDL‐C obtained by the formula. In rats whose serum cholesterol was <100 mg/dL, or whose HDL‐C constituted ≥75% of total cholesterol, or whose cholesterol/phospholipids ratio was <1, or whose serum did not contain β‐VLDL, LDL‐C obtained by both methods did not significantly differ. Under other conditions, however, and particularly in hypercholesterolaemic rats who did present β‐VLDL, the results clearly show that the Friedewald formula overestimates LDL‐C levels. In conclusion, (VLDL + LDL)‐C instead of VLDL‐C and LDL‐C must be used when ultracentrifugation or other alternative methods are not available to measure LDL‐C in hypercholesterolaemic rats.     

Consumption of High-Oleic Soybean Oil Improves Lipid and Lipoprotein Profile in Humans Compared to a Palm Oil Blend: A Randomized Controlled Trial

Partially hydrogenated oils (PHO) have been removed from the food supply due to adverse effects on risk for coronary heart disease (CHD). High-oleic soybean oils (HOSBO) are alternatives that provide functionality for different food applications. The objective of this study was to determine how consumption of diets containing HOSBO compared to other alternative oils, with similar functional properties, modifies LDL cholesterol (LDLc) and other risk factors and biomarkers of CHD. A triple-blind, crossover, randomized controlled trial was conducted in humans (n = 60) with four highly-controlled diets containing (1) HOSBO, (2) 80:20 blend of HOSBO and fully hydrogenated soybean oil (HOSBO+FHSBO), (3) soybean oil (SBO), and (4) 50:50 blend of palm oil and palm kernel oil (PO + PKO). Before and after 29 days of feeding, lipids/lipoproteins, blood pressure, body composition, and markers of inflammation, oxidation, and hemostasis were measured. LDLc, apolipoprotein B (apoB), NonHDL-cholesterol (HDLc), ratios of total cholesterol (TC)-to-HDLc and LDLc-to-HDL cholesterol, and LDL particle number and small LDL particles concentration were lower after HOSBO and HOSBO+FHSBO compared to PO (specific comparisons p < 0.05). Other than TC:HDL, there were no differences in lipid/lipoprotein markers when comparing HOSBO+FHSBO with HOSBO. LDLc and apoB were higher after HOSBO compared to SBO (p < 0.05). PO + PKO increased HDLc (p < 0.001) and apolipoprotein AI (p < 0.03) compared to HOSBO and HOSBO+FHSBO. With the exception of lipid hydroperoxides, dietary treatments did not affect other CHD markers. HOSBO, and blends thereof, is a PHO replacement that results in more favorable lipid/lipoprotein profiles compared to PO + PKO (an alternative fat with similar functional properties).     

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans

The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however, FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P<0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P<0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL₂/HDL₃ cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.     

The influence of plasma apolipoprotein A‐II concentrations on HDL subclass distribution

Background and aims: To investigate the impact of plasma apoA‐II concentrations on the alteration of HDL subclass distribution, and the cooperative effect of apoA‐I and apoA‐II on it. Methods and results: The apoA‐I contents of plasma HDL subclasses were quantified by two‐dimensional gel electrophoresis associated with immunodetection for 292 Chinese people. These subjects were divided according to the mean ± 1 SD of apoA‐II and apoA‐I levels as two cut‐points, respectively. Compared with the low‐apoA‐II group, the apoA‐I contents of HDL_3a (in the high group), HDL_3b, and HDL_2b increased strikingly, both in the middle‐ and high‐apoA‐II group. The apoA‐I contents of all HDL subclasses increased progressively when the apoA‐I and apoA‐II levels simultaneously or the apoA‐I/apoA‐II ratio increased, and in comparison to the low‐apoA‐I–A‐II levels group, the apoA‐I contents of HDL_2b (115%) increased more significantly than those of preβ₁‐HDL (39%) in the high‐apoA‐I–A‐II levels group. Multiple analyses also indicated that the three HDL subclasses, HDL_3a, HDL_3b and HDL_2b, were independently predicted by apoA‐II. Conclusion: Excess apoA‐II can cause the accumulation of both large‐sized HDL_2b and small‐sized HDL₃, which implies that apoA‐II plays a double role in the HDL maturation metabolism. Meanwhile, the degree of HDL_2b increased significantly relative to that of preβ₁‐HDL when apoA‐I and apoA‐II levels were elevated simultaneously, suggesting that the maturation and metabolism of HDL might be promoted and reverse cholesterol transport might be enhanced.     

n-3 fatty acids and lipoproteins: Comparison of results from human and animal studies

The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of n-3 FA on blood lipoproteins in 72 placebo-controlled human trials, at least 2 wk in length and providing 7 or less g of n-3 FA/day. Trials in normolipidemic subjects (triglycerides <2.0 mM; 177 mg/dL) were compared to those in hypertriglyceridemic patients (triglycerides ≥2.0 mM). In the healthy subjects, mean triglyceride levels decreased by 25% (P<0.0001), and total cholesterol (C) levels increased by 2% (P<0.009) due to the combined increases in low density lipoprotein (LDL)-C (4%,P<0.02) and high density lipoprotein (HDL)-C (3%,P<0.008). In the patients, triglyceride levels decreased by 28% (P<0.0001), LDL-C rose by 7% (P<0.0001), but neither total C nor HDL-C changed significantly. Although the effect on triglyceride levels is also observed in rats and swine, it is rarely seen in mice, rabbits, monkeys, dogs, and hamsters. Whereas n-3 FA have only a minor impact on lipoprotein C levels in humans, they often markedly lower both total C and HDL-C levels in animals, especially monkeys. These differences are not widely appreciated and must be taken into account when studying the effects of n-3 FA on lipoprotein metabolism.     

Low-Density Lipoproteins,High-Density Lipoproteins (HDL), and HDL-Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), high-density lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells—a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose- and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5′-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.     

Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

The catabolism and structure of high‐density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A‐I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL‐apo A‐I was evaluated by exogenous radiolabelling with iodine‐131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol‐to‐phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [¹³¹I]‐apo A‐I in the proteinuric rabbits was faster (FCR = 0.036 h^?1) compared to control rabbits group (FCR = 0.026 h^?1, P < 0.05). Apo E increased and apo A‐I decreased in HDL, whereas PON‐1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase‐1 activity, and a rise in the fractional catabolic rate of the [¹³¹I]‐apo A‐I.