Functional Properties Of High-density Lipoprotein Research Articles

Compositional and functional properties of high-density lipoproteins in relation to coronary in-stent restenosis.

In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study.

Prolonged bedrest reduces plasma high-density lipoprotein levels linked to markedly suppressed cholesterol efflux capacity

Recent observations strongly connect high-density lipoproteins (HDL) function and levels with coronary heart disease outcomes and risk for infections and sepsis. To date, our knowledge of factors determining this connection is still very limited. The immobility associated with prolonged bedrest is detrimental to health, affecting several systems, including the cardiovascular, pulmonary, gastrointestinal, musculoskeletal and urinary. Effects of prolonged bedrest on the composition and functional properties of HDL remain elusive. We evaluated metrics of HDL composition and function in healthy male volunteers participating in a randomized, crossover head-down bedrest study. We observed that HDL cholesterol efflux capacity was profoundly decreased during bedrest, mediated by a bedrest associated reduction in plasma levels of HDL-cholesterol and major apolipoproteins (apo) apoA-I and apoA-II. Paraoxonase activity, plasma anti-oxidative capacity and the activities of lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein were not affected. No change was observed in the content of HDL-associated serum amyloid A, a sensitive marker of inflammation. Resistive vibration exercise countermeasure during bedrest did not correct impaired cholesterol efflux capacity and only tended to increase arylesterase activity of HDL-associated paraoxonase. In conclusion, prolonged bedrest reduces plasma HDL levels linked to markedly suppressed HDL cholesterol efflux capacity. Resistive vibration exercise during bedrest did not correct HDL levels and impaired cholesterol efflux capacity.

Endothelial lipase increases eNOS activating capacity of high-density lipoprotein

Endothelial lipase (EL) changes structural and functional properties of high-density lipoprotein (HDL). HDL is a relevant modulator of endothelial nitric oxide synthase (eNOS) activity, but the effect of EL on HDL induced eNOS-activation has not yet been investigated. Here, we examined the impact of EL-modified HDL (EL-HDL) on eNOS activity, subcellular trafficking, and eNOS- dependent vasorelaxation. EL-HDL and empty virus (EV)-HDL as control were isolated from human serum incubated with EL-overexpressing or EV infected HepG2 cells. EL-HDL exhibited higher capacity to induce eNOS phosphorylation at Ser1177 and eNOS activity in EA.hy 926 cells, as well as eNOS-dependent vasorelaxation of mouse aortic rings compared to control HDL. As revealed by confocal and structured illumination-microscopy EL-HDL-driven induction of eNOS was accompanied by an increased eNOS-GFP targeting to the plasma membrane and a lower eNOS-GFP colocalization with Golgi and mitochondria. Widefield microscopy of filipin stained cells revealed that EL-HDL lowered cellular free cholesterol (FC) and as found by thin-layer chromatography increased cellular cholesterol ester (CE) content. Additionally, cholesterol efflux capacity, acyl-coenzyme A: cholesterol acyltransferase activity, and HDL particle uptake were comparable between EL-HDL and control HDL. In conclusion, EL increases eNOS activating capacity of HDL, a phenomenon accompanied by an enrichment of the plasma membrane eNOS pool, a decreased cell membrane FC and increased cellular CE content.

Endothelial lipase increases antioxidative capacity of high-density lipoprotein

Endothelial lipase (EL) is a strong determinant of structural and functional properties of high-density lipoprotein (HDL). We examined whether the antioxidative capacity of HDL is affected by EL. EL-modified HDL (EL-HDL) and control EV-HDL were generated by incubation of HDL with EL- overexpressing or control HepG2 cells. As determined by native gradient gel electrophoresis, electron microscopy, and small-angle X-ray scattering EL-HDL is smaller than EV-HDL. Mass spectrometry revealed an enrichment of EL-HDL with lipolytic products and depletion of phospholipids and triacylglycerol. Kinetics of conjugated diene formation and HPLC-based malondialdehyde quantification revealed that EL-HDL exhibited a significantly higher resistance to copper ion-induced oxidation and a significantly higher capacity to protect low-density lipoprotein (LDL) from copper ion-induced oxidation when compared to EV-HDL. Depletion of the lipolytic products from EL-HDL abolished the capacity of EL-HDL to protect LDL from copper ion-induced oxidation, which could be partially restored by lysophosphatidylcholine enrichment. Proteomics of HDL incubated with oxidized LDL revealed significantly higher levels of methionine 136 sulfoxide in EL-HDL compared to EV-HDL. Chloramine T (oxidizes methionines and modifies free thiols), diminished the difference between EL-HDL and EV-HDL regarding the capacity to protect LDL from oxidation. In absence of LDL small EV-HDL and EL-HDL exhibited higher resistance to copper ion-induced oxidation when compared to respective large particles. In conclusion, the augmented antioxidative capacity of EL-HDL is primarily determined by the enrichment of HDL with EL-generated lipolytic products and to a lesser extent by the decreased HDL particle size and the increased activity of chloramine T-sensitive mechanisms.

Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein

Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.

Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery

Background and aimsAlthough the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. MethodsThis study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. ResultsIn the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. ConclusionsWe identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.

Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study

Background and aimsAlthough low high-density lipoprotein (HDL) cholesterol concentration is an established risk factor for coronary heart disease (CHD), information regarding subtypes of stroke is very limited, especially in Asian populations. MethodsA prospective study was conducted among 30,736 individuals aged 40–69 years, who lived in nine communities in Japan and did not have a history of cardiovascular disease (CVD). CHD and stroke, including its subtypes, were assessed, and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated according to quintiles of HDL cholesterol using Cox proportional models adjusted for other CVD risk factors. ResultsWe identified 296 CHD and 1712 stroke events over a median 15 yr of follow-up. HDL cholesterol concentration showed an inverse association with CHD in men and women. A low HDL cholesterol concentration slightly raised the risk for total strokes in men, but not in women. When analyzed by subtypes, we observed an inverse relationship between HDL cholesterol concentration and the incidence of lacunar infarction, with an adjusted HR for the lowest quintile of HDL cholesterol concentration compared with the highest quintile of 1.63 (95% CI, 1.00–2.66) in men and 1.97 (95% CI, 1.19–3.26) in women. HDL cholesterol concentration was positively associated with the risk of intracerebral hemorrhage (ICH) in a linear manner in women (p for trend = 0.028), but not in men. ConclusionsThe associations of HDL cholesterol concentration with lacunar infarction and ICH may be related to different functional properties of HDL rather than to its protective function against lipid-rich atherosclerosis.

Anti-atherogenic properties of high-density lipoproteins in psychiatric patients before and after two months of atypical anti-psychotic therapy.

Some of the medications used for the management of schizophrenia are associated with clinically significant increases in weight and adverse alterations in serum lipid levels. The aim of the study was to investigate the effect of short-term (two months) treatment with atypical anti-psychotics on coronary heart disease risk factors, including the functional properties of high-density lipoprotein (HDL), in psychiatric patients. Nineteen patients diagnosed with schizophrenia, schizoaffective, and bipolar disorder and ten healthy volunteers were enrolled in the study. In the present study blood was drawn at baseline and after two months of atypical anti-psychotic treatment. Wilcoxon non-parametric-test was used to examine differences in the psychotic group before and two months after treatment.Waist circumference and oxidative stress in psychiatric patients were higher compared with the control group. Serum-mediated cholesterol efflux capacity was lower in psychotic patients compared to controls. Two months of anti-psychotic therapy was associated with increased abdominal obesity, decreased paraoxonase lactonase activity, but with no further change in serum-mediated cholesterol efflux from macrophages. Psychotic patients have low serum-mediated cholesterol efflux from macrophages as a parameter of HDL functionality. Atypical anti-psychotic treatment for two months increased metabolic derangements in these patients but without further decrement in serum-mediated cholesterol efflux.

A high throughput biochemical fluorometric method for measuring lipid peroxidation in HDL.

Current cell-based assays for determining the functional properties of high-density lipoproteins (HDL) have limitations. We report here the development of a new, robust fluorometric cell-free biochemical assay that measures HDL lipid peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox correlated with previously validated cell-based (r = 0.47, p<0.001) and cell-free assays (r = 0.46, p<0.001). HDLox distinguished dysfunctional HDL in established animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients. Using an immunoaffinity method for capturing HDL, we demonstrate the utility of this novel assay for measuring HDLox in a high throughput format. Furthermore, HDLox correlated significantly with measures of cardiovascular diseases including carotid intima media thickness (r = 0.35, p<0.01) and subendocardial viability ratio (r = −0.21, p = 0.05) and physiological parameters such as metabolic and anthropometric parameters (p<0.05). In conclusion, we report the development of a new fluorometric method that offers a reproducible and rapid means for determining HDL function/quality that is suitable for high throughput implementation.

The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality.

The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL's anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL's protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL's biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.

Simvastatin and bezafibrate increase cholesterol efflux in men with type 2 diabetes

The importance of functional properties of high-density lipoproteins (HDL) for atheroprotection is increasingly recognized. We determined the impact of lipid-lowering therapy on 3 key HDL functionalities in Type 2 diabetes mellitus (T2DM). A placebo-controlled, randomized cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), alone and in combination) was carried out in 14 men with T2DM. Cholesterol efflux was determined using human THP-1 monocyte-derived macrophages, HDL antioxidative capacity was measured as inhibition of low-density lipoprotein oxidation in vitro, and HDL anti-inflammatory capacity was assessed as suppression of thrombin-induced monocyte chemotactic protein 1 expression in human umbilical vein endothelial cells. Pre-β-HDL was assayed using crossed immunoelectrophoresis. While cholesterol efflux increased in response to simvastatin, bezafibrate and combination treatment (+12 to +23%; anova, P = 0.001), HDL antioxidative capacity (P = 0.23) and HDL anti-inflammatory capacity (P = 0.15) did not change significantly. Averaged changes in cellular cholesterol efflux during active treatment were correlated positively with changes in HDL cholesterol, apoA-I and pre-β-HDL (P < 0.05 to P < 0.001). There were no inter-relationships between changes in the three HDL functionalities during treatment (P > 0.10). Changes in HDL antioxidative capacity and anti-inflammatory capacity were also unrelated to changes in HDL cholesterol and apoA-I, while changes in HDL antioxidative capacity were related inversely to pre-β-HDL (P < 0.05). Simvastatin and bezafibrate increase cholesterol efflux, parallel to HDL cholesterol and apoA-I responses. The antioxidative and anti-inflammatory properties of HDL are not to an important extent affected by these therapeutic interventions.

Assessing the Functional Properties of High-Density Lipoproteins: An Emerging Concept in Cardiovascular Research

Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL cholesterol mass levels, the functionality of HDL particles is increasingly regarded as potentially clinically important. This review provides an overview of four key functional properties of HDL, namely cholesterol efflux and reverse cholesterol transport; antioxidative activities; anti-inflammatory activities; and the ability of HDL to increase vascular nitric oxide production resulting in vasorelaxation. Currently available assays are put into context with different HDL isolation procedures yielding compositional heterogeneity of the particle. Gathered knowledge on the impact of different disease states on HDL function is discussed together with potential underlying causative factors modulating HDL functionalities. In addition, a perspective is provided regarding how a better understanding of the determinants of (dys)functional HDL might impact clinical practice and the future design of rational and specific therapeutic approaches targeting atherosclerotic cardiovascular disease.

Treating High Density Lipoprotein Cholesterol (HDL-C): Quantity Versus Quality

Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease (CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular disease. However, despite the efficacy of statins in reducing cardiovascular morbidity and mortality, a significant residual risk has been observed even after reaching the LDL-C target, suggesting that other risk factors beyond LDL-C should be addressed, including low levels of HDL-cholesterol (HDL-C). Several clinical trials have shown an inverse relationship between HDL-C levels and cardiovascular risk, and 1 mg/dl increment in HDL-C is associated in epidemiological studies with a 2-3% decrease in cardiovascular risk, suggesting that raising HDL-C levels might have beneficial effects to reduce cardiovascular disease. However, several lines of evidence indicate that the functional properties of HDL may be relevant as well. In patient with CAD and normal HDL-C levels, HDL exhibit significantly reduced protective functions, and rather appear to be pro-atherogenic; on the other hand some genetic mutations causing low levels of HDL-C are not associated with increased atherosclerosis. Furthermore, although niacin significantly increased HDL-C levels, no further clinical benefit was observed from the addition of niacin to statin therapy, suggesting that increasing HDL-C levels is not sufficient and perhaps functional properties of HDL must be considered when choosing a therapeutic strategy to reduce the residual cardiovascular risk.

Dietary approaches to improving atheroprotective HDL functions

High-density lipoproteins (HDL) are known to protect against cardiovascular disease (CVD). In addition to facilitating reverse cholesterol transport to remove excess lipids from the body - including atherosclerotic plaques - HDL exhibits antioxidant, anti-inflammatory, vasodilatory, and antithrombotic activities. Together, these properties contribute to the overall atheroprotective nature of HDL. However, similar to many other physiological pathways, these HDL parameters are known to become dysregulated in conditions of metabolic disease. Further, research suggests these alternative HDL properties may be regulated independently of blood HDL-cholesterol (HDL-C) levels, and must therefore be considered when designing HDL-targeted therapies. To date, a number of dietary strategies have been investigated to assess the effect of dietary components on functional properties of HDL beyond HDL-C. This review will highlight the bioactive nutrients, functional foods, and dietary programs known to modulate HDL function as a means of reducing CVD.

Apolipoprotein A-II-mediated Conformational Changes of Apolipoprotein A-I in Discoidal High Density Lipoproteins

It is well accepted that HDL has the ability to reduce risks for several chronic diseases. To gain insights into the functional properties of HDL, it is critical to understand the HDL structure in detail. To understand interactions between the two major apolipoproteins (apos), apoA-I and apoA-II in HDL, we generated highly defined benchmark discoidal HDL particles. These particles were reconstituted using a physiologically relevant phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) incorporating two molecules of apoA-I and one homodimer of apoA-II per particle. We utilized two independent mass spectrometry techniques to study these particles. The techniques are both sensitive to protein conformation and interactions and are namely: 1) hydrogen deuterium exchange combined with mass spectrometry and 2) partial acetylation of lysine residues combined with MS. Comparison of mixed particles with apoA-I only particles of similar diameter revealed that the changes in apoA-I conformation in the presence of apoA-II are confined to apoA-I helices 3-4 and 7-9. We discuss these findings with respect to the relative reactivity of these two particle types toward a major plasma enzyme, lecithin:cholesterol acyltransferase responsible for the HDL maturation process.

The effect of poloxamer 407 on the functional properties of HDL in mice

There is an inverse relationship between high-density lipoprotein (HDL) and heart disease. HDL possesses not only both antioxidant and anti-inflammatory properties, but also anti-thrombotic and endothelial function-promoting qualities. However, it is not only the serum concentration of HDL that is important, but also the 'functional' quality of the HDL. The objective was to determine the functional status of HDL in a well-established mouse model of dyslipidaemia and atherosclerosis induced by the administration of a block copolymer (poloxamer 407; P-407). C57BL/6 mice were administered a single intraperitoneal dose of P-407 (0.5g/kg) and blood was collected at 24h post-dosing. HDL was isolated from controls (control HDL) and P-407-treated (P-407 HDL) mice and used to test its anti-inflammatory properties in vitro. Additionally, antioxidant enzymes associated with HDL, namely, platelet activating factor-acetylhydrolase (PAF-AH) and paraoxonase (PON), were evaluated for any potential reduction in their biological activity. A single injection of P-407 in C57BL/6 mice resulted in a marked decrease in the levels of HDL-cholesterol and phospholipids. HDL particle size significantly increased, primarily due to remodelling of HDL with triglyceride. It was demonstrated that (i) long-chain saturated fatty acids were higher and the n-3/n-6 fatty acid ratio was significantly lower for P-407 HDL compared with control HDL, and (ii) P-407 HDL lost its capacity to inhibit tumour necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expression compared with control HDL. Additionally, P-407 HDL was not able to neutralize lipopolysaccharide and inhibit subsequent TNF-α production compared with control HDL. The biological activity of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase (PON) decreased in direct proportion to the circulating levels of both HDL-cholesterol and apolipoprotein (apoA-1). Combination of previously reported findings in P-407-treated mice, such as (i) production of both oxidized LDL and malondialdehyde, and (ii) profound elevations in the soluble forms of intercellular adhesion molecule-1 (ICAM-1), VCAM-1, and E-selectin, with the present results, would strongly suggest that HDL in P-407-treated mice is rendered dysfunctional. Thus, these findings help to explain why P-407-treated mice begin to form aortic atherosclerotic lesions about one month after initiating P-407 treatment.

L 001 Changes in the Functional Properties of High-Density Lipoprotein (HDL) and the Cholesteryl Esters and Phospholipids Transfer Proteins Activities in Hamsters Submitted to Hiperlipidemic Diet

L 001 Changes in the Functional Properties of High-Density Lipoprotein (HDL) and the Cholesteryl Esters and Phospholipids Transfer Proteins Activities in Hamsters Submitted to Hiperlipidemic Diet

L 027 Changes in the Functional Properties of High-density Lipoprotein (HDL) in Hamsters Submitted to Dietary Supplementation with Saturated, Monounsaturated or Polyunsaturated Fatty Acid-Rich Oils

La variabilidad individual de la respuesta lipémica posprandial excede a la que se produce en la lipemia del ayuno, debido a la influencia de factores ambientales y genéticos. Uno de los factores ambientales más relevantes es el tipo de alimentación habitual de las personas. El consumo de dietas ricas en grasa saturada favorece un mayor aumento de partículas ricas en triglicéridos posprandiales que con el consumo de dietas muy pobres en grasa y de dietas ricas en grasa poliinsaturada n-3. Sin embargo, son pocos los estudios que investiguen el efecto de la grasa monoinsaturada sobre los valores de lípidos plasmáticos en estado posprandial. Por consiguiente, nuestro objetivo fue analizar el efecto agudo de la ingesta de distintos tipos de grasa sobre la lipemia posprandial.La población a estudiar consistió en 21 voluntarios varones jóvenes sanos y con una edad media de 23 años a los que se sometieron a 3 sobrecargas grasas con vitamina A. La composición de la sobrecarga grasa fue de 1 g de grasa/kg de peso (el 65% grasa) con diferente composición grasa y siguiendo un protocolo aleatorizado y cruzado. La composición de las 3 sobrecargas grasas fue la siguiente: comida rica en ácidos grasos monoinsaturados procedente del aceite de oliva (un 22% de grasas saturadas, un 38% de ácidos grasos monoinsaturados, un 4% de ácidos grasos poliinsaturados y un 0,7% de ácido α-linolénico); comida rica en grasa saturada (un 38% de grasas saturadas, un 22% de ácidos grasos monoinsaturados, un 4% de ácidos grasos poliinsaturados y un 0,7% de ácido α-linolénico), y por último, una comida rica en ácidos grasos poliinsaturados n-3 de origen vegetal (un 20% de grasas saturadas, un 24% de ácidos grasos monoinsaturados, un 16% de ácidos grasos poliinsaturados y un 4% de ácido α-linolénico). Se extrajo sangre venosa en el tiempo 0 y a las 2, 4, 6 y 8,5 h. Se determinaron los valores plasmáticos de triglicéridos, colesterol total, lipoproteínas de alta densidad, lipoproteínas de baja densidad y apolipoproteínas A-I y B.Se observó una mayor concentración de triglicéridos en el tiempo 2, con la comida rica en aceite de oliva que con las grasas saturada y poliinsaturada, rica en nueces. En el tiempo 8 se encontró una menor concentración de triglicéridos tras la sobrecarga rica en aceite de oliva comparada con la rica en nueces. No hubo cambios para el resto de partículas lipídicas estudiadas.Las personas mostraron una cinética de aclaramiento distinta en los valores de triglicéridos posprandiales tras la comida rica en aceite de oliva en comparación con la comida rica en grasa saturada y poliinsaturada n-3.Because of environmental and genetic factors, individual variability in postprandial lipemic response is greater than that produced in fasting lipemia. One of the most important environmental factors is the individual's normal diet. Diets rich in saturated fatty acids (SAFA) favor a greater increase in postprandial triglyceride (TG)-rich particles than low-fat diets and those rich in polyunsaturated N-3 fatty acids (PUFA). However, few studies have investigated the effect of monounsaturated fatty acids (MUFA) on plasma lipid levels in the postprandial state.Consequently, the aim of this study was to analyze the acute effect of intake of distinct types of fat on postprandial lipemia.Twenty-one healthy male volunteers with a mean age of 23 years underwent three vitamin A-fat load tests consisting of 1 g of fat/kg body weight (65% fat) with distinct fat compositions, following a randomized, crossover protocol. The composition of the diets was: high-MUFA diet from olive oil (22% SAFA, 38%; MUFA, 4%; PUFA, 0.7%; α-linolenic acid); high-SAFA diet (38% SAFA; 22% MUFA, 4% PUFA, 0.7% α-linolenic acid); PUFA-rich diet from vegetable fats (20% SAFA, 24% MUFA, 16% PUFA, 4% α-linolenic acid). Blood samples were taken at 0, 2, 4, 6, and 8.5 hours. Plasma TG, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein (Apo) A-I and Apo B were determined.TG concentration was greater at 2 hours the after intake of food rich in olive oil than after the intake of saturated and polyunsaturated fats, rich in nuts. At 8 hours, TG concentration was lower after the intake of food rich in olive oil than after the intake of polyunsaturated fat, rich in nuts. No changes in total cholesterol, HDL, LDL, Apo A-I or Apo B were observed.The kinetics of TG clearance differed after the monounsaturated fat load test compared with polyunsaturated N-3 and saturated fat loads.

Impact of freezing on high-density lipoprotein functionality

Structural and functional properties of high-density lipoprotein (HDL) after short-term freezing in the presence or absence of 10% sucrose were compared with HDL stored at 4 °C. Freezing did not affect the size of HDL particles or their antiinflammatory and antioxidant properties. Freezing slightly impaired the ability of HDL to support cholesterol efflux from human macrophages, but this property was preserved when HDL was frozen in the presence of sucrose. Freezing also resulted in approximately 10% loss of HDL in the samples. We conclude that freezing HDL in the presence of 10% sucrose preserves its structural and functional properties.

The two faces of the 'good' cholesterol.

Although a low level of high-density lipoprotein (HDL) cholesterol is a useful clinical predictor of coronary heart disease, raising the HDL cholesterol level does not necessarily lower this risk. Part of the explanation for this paradox may be that, under certain conditions, HDL either can be less functional as an antioxidant or can even enhance the oxidation and inflammation associated with atherosclerotic plaque. Thus, the functional properties of HDL--not simply the level--may need to be considered and optimized.