The Value and Distribution of High-Density Lipoprotein Subclass in Patients with Acute Coronary Syndrome

Background

High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS.

Methods

Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography.

Results

The small-sized preβ₁-HDL, HDL_3b, and HDL_3a levels were significantly higher, and the large-sized HDL_2a and HDL_2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL_2b contents significantly decreased and the preβ₁-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL_2a, and HDL_2b. Moreover, the FPG levels were positively related to HDL_3c, HDL_3b, and HDL_3a in ACS patients.

Conclusion

The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.     

Effects of heparin infusion on plasma lipoproteins in subjects with lipoprotein lipase deficiency: Evidence for a role of hepatic endothelial lipase in the metabolism of high-density lipoprotein subfractions in man

The role of heparin-releasable hepatic endothelial lipase (HL) in human plasma lipoprotein metabolism was investigated by examining the effects of intravenous infusion of heparin (180 units/kg over 2 h) in 8 subjects with primary extrahepatic lipoprotein lipase deficiency. In addition to reducing the triglyceride concentration in very low-density lipoproteins, heparin-induced release of HL reduced the phopholipid and protein concentrations in the HDL₂ subclass of high-density lipoprotein (by 28% and 36% respectively, mean values) and simultaneously increased the HDL₃ phospholipid concentration (by 23%), providing the first in vivo evidence for a function of HL in the interconversion of the major HDL subfractions in man.     

Plasma factors affecting the in vitro conversion of high-density lipoproteins labeled with a non-transferable marker

We studied the in vitro conversion of HDL₃ labeled with a radioiodinated diacyl lipid associating peptide (diLAP). DiLAP was previously shown to be nontransferable, which permitted its' use as a reliable marker of HDL particles. DiLAP-labeled HDL₃ was incubated for 23 h at 37°C in human or rat plasma or in reconstituted media containing delipidated plasma and/or lipoproteins and/or partially purified CETP. At the end of the incubations, the samples were adjusted to a density of 1.125 g/ml and ultracentrifuged. The two resulting fractions containing HDL₂ and HDL₃, respectively, were analyzed by gradient gel electrophoresis. Depending upon experimental conditions, diLAP-labeled HDL₃ was converted into HDL_2b- and/or small HDL_3c-like particles. LCAT inhibition and to a lesser extent CETP promoted the formation of small HDL_3c. Reactivation of LCAT led to the disappearance of small HDL_3c. No HDL_3c formed from HDL₂ even in the absence of LCAT activity. When the incubations were performed in the presence of 100 mM thimerosal, which inhibited PLTP but not CETP activity, the conversion of diLAP-labeled HDL₃ into HDL₂ was almost completely blocked. Collective consideration of these data indicates that the formation of small HDL is moderately facilitated by CETP; that small HDL are converted to larger HDL species by LCAT and that the transformation of HDL₃ into HDL₂ is a process which largely depends upon PLTP activity.     

Rates of cholesterol exchange between human erythrocytes and plasma lipoproteins

Rates of exchange of labelled cholesterol between human erythrocytes and three plasma lipoprotein species, LDL, HDL₂ and HDL₃, were measured over a range of lipoprotein concentrations and temperatures. The exchange rates reached limiting, concentration-independent values, which were the same for the three lipoproteins. The temperature dependencies correspond to activation energies of 12 kcal in the limiting rate region, and at lower lipoprotein concentrations to activation energies of 11 to 22 kcal. Calculations based on simple collision theory indicate that energetic barriers to the exchange are far smaller than indicated by these activation energies and that no particular orientation of lipoprotein molecules is required for the exchange. The occurrence of a limiting rate may be a result of the adsorption of lipoprotein molecules onto a limited number of sites on the cell surface, or of a slow process occurring in the membrane, possibly the diffusion of cholesterol. Present data do not permit a choice between these models.     

Separation of the principal HDL subclasses by iodixanol ultracentrifugation

HDL subclasses detection, in cardiovascular risk, has been limited due to the time-consuming nature of current techniques. We have developed a time-saving and reliable separation of the principal HDL subclasses employing iodixanol density gradient ultracentrifugation (IxDGUC) combined with digital photography. HDL subclasses were separated in 2.5 h from prestained plasma on a three-step iodixanol gradient. HDL subclass profiles were generated by digital photography and gel scan software. Plasma samples (n = 46) were used to optimize the gradient for the resolution of HDL heterogeneity and to compare profiles generated by IxDGUC with gradient gel electrophoresis (GGE); further characterization from participants (n = 548) with a range of lipid profiles was also performed. HDL subclass profiles generated by IxDGUC were comparable to those separated by GGE as indicated by a significant association between areas under the curve for both HDL₂ and HDL₃ (HDL₂, r = 0.896, P < 0.01; HDL₃, r = 0.894, P < 0.01). The method was highly reproducible, with intra- and interassay coefficient of variation percentage < 5 for percentage area under the curve HDL₂ and HDL₃, and < 1% for peak Rf and peak density. The method provides time-saving and cost-effective detection and preparation of the principal HDL subclasses.     

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferae reactivity

Human HDL₃ (d 1.125−1.21 g/ml) were treated by an exogenous phospholipase A₂ from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products.

• 1.(1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5–10% haematocrit and HDL₃ (0.6 mM total cholesterol) from 0 to 12–15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 μM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL.
• 2.(2) The lecithin: cholesterol acyltransferase reactivity of HDL₃, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A₂ treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21–1.25 g /ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15–30% lipolysis, the lecithin:cholesterol acyltransferase reactivity of HDL₃ was reduced about 30–40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle.
• 3.(3) The addition of the lecithin:cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL₃ promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin:cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin:cholesterol acyltransferase-induced removal of cellular cholesterol.

     

Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps

Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL₂ and HDL₃ (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries.     

Lipid profile of a French-Canadian population: 1. Association of plasma lipid and lipoprotein levels with age,relative body weight and education

Plasma lipid and lipoprotein levels were determined in a randomly selected population of 1169 French-Canadian men in the Quebec City area. The mean levels of total plasma cholesterol and triglycerides were 224.0 and 166.5 mg/dL respectively. The mean level of low-density lipoprotein cholesterol was higher and the mean level of high-density lipoprotein (HDL) cholesterol lower than those reported in a recent study in English-Canadian men. The mean HDL₂ and HDL₃ levels were lower than those reported in American men. Stratification of plasma triglyceride levels for all age groups showed that mean HDL₂ levels decreased rapidly with moderate rises in triglyceride levels. Less than 9% of the variation in lipid or lipoprotein levels was related to age or relative body weight. Education had no significant effect on the levels.     

Inhibition par les lipoprotéines de haute densité HDL2 et HDL3 de la synthèse du DNA et des stérols des lymphocytes humains stimulés par la concanavaline A.

Lipoproteins HDL₂ and HDL₃ inhibit DNA synthesis and sterol synthesis in human Con A-stimulated lymphocytes cultured in a medium supplemented with 20 per cent lipoprotein deficient serum. On the basis of the amount of proteins added, HDL₂ is more efficient on DNA and sterol synthesis than HDL₃ and less efficient than LDL. However, on the basis of the amount of cholesterol added, the inhibition of sterol synthesis induced by these three lipoproteins is not significantly different. At all concentrations of these three lipoproteins, the inhibition of sterol synthesis is higher than the inhibition of DNA synthesis.     

Structure of human serum lipoproteins in solution. II. Small-angle x-ray scattering study of HDL and LDL.

Two human serum lipoprotein particles, HDL₃ and LDL, were studied in solution in solvents of variable density (NaBr in water) by small-angle X-ray scattering using a position-sensitive proportional counter. The data were analysed using the theoretical approach outlined in the accompanying paper (Luzzati et al., 1976). The structures of the particles were found to be independent of the salt concentration of the solution (i.e. the particles are impenetrable to NaBr). Density heterogeneities are negligible and size and shape heterogeneities appear to be small.The particle structures could be quantitatively described in terms of a set of parameters and of a few one-dimensional functions. The parameters are the volume, radius of gyration and surface area of the shape functions; the second moment and square average of the electron density contrast at buoyancy; the electron density level, volume, radius of gyration and surface area of the hydrocarbon and polar regions. The one-dimensional functions are: the distribution of chords, the spherical average of the shape function and of the electron density at buoyancy, and the fraction of each spherical shell occupied by the hydrocarbon and polar regions. These parameters and functions are internally consistent and agree with the chemical data confirming the assumptions made in their derivation.The results are compatible with the shape of the particle being compact and quasi-spherical although with deeply convoluted surfaces. They also indicate that the outer layers of the particles are occupied by the proteins and the polar groups of phospholipids and free cholesterol, and the cores by neutral lipids. The maximum diameters of the particles are 130Å and 280Å for HDL₃ and LDL, respectively, while the hydrocarbon cores have diameters of 80Å and 230Å, respectively. The solvent is considered to penetrate to 25Å from the center of the HDL₃ particle with a minimum solvation at a radius of 45Å. In the case of LDL, the solvent penetrates to 55Å from the center of the particle. The lipids in the cores of the particles, particularly the cholesterol esters, appear to display a micelle-like organization with the steroid nuclei segregated in regions distinct from those occupied by the hydrocarbon chains.Although the data are consistent with several aspects of previously proposed models, they indicate that the structures of the HDL₃ and LDL particles are more complex than previously believed.     

On the Ability of High Density Lipoproteins to Remove Phospholipid Peroxidation Products from Erythrocyte Membranes

To study the transfer of oxidized phospholipids from cell membranes to high-density lipoproteins (HDL), human Cu²⁺-oxidized erythrocyte membranes were incubated with HDL₃ subfraction for 17 h at 37°C followed by isolation of the supernatant, precipitation from it of HDL₃, and determination of lipid peroxide products (LPP) in them. The incubation increased the content of lipid hydroperoxides in HDL₃ significantly (by 32 and 40% calculated per ml of sample or mg of protein) and of malondialdehyde (by 27 and 34%, respectively) compared to control (incubation of HDL₃ alone). The content of conjugated dienes did not change significantly. Fluorescence analyses of isolated HDL₃ particles showed that the content of fluorescent products (_ex = 365 nm, _em = 430 nm) in them was 2.5 times higher than in control, and the number of binding sites for the 1-anilinonaphthalene-8-sulfonic acid probe decreased by 22%. This also confirms accumulation of LPP in the lipoprotein subfraction. It seems likely that an increase in LPP (at least hydroperoxides) in HDL₃ after their incubation with oxidized membranes occurs via transport of phospholipids containing LPP from erythrocyte membranes to lipoproteins. The data on the ability of HDL₃ to accept LPP from erythrocyte membranes in vitro suggest that HDL₃ may have a protective action on cell membranes undergoing oxidation in vivo as well.     

Effects of high-density lipoprotein2 on cholesterol transport and acyl-coenzyme A:cholesterol acyltransferase activity in P388D1 macrophages

High-density lipoproteins are the putative vehicles for cholesterol removal from monocyte-derived macrophages, which are an important cell type in all stages of atherosclerosis. The role of HDL₂, an HDL subclass that accounts for most variation in plasma HDL-cholesterol concentration, in cholesterol metabolism in monocyte-derived macrophages is not known. In this study, the dose-dependent effects of HDL₂ on cellular cholesterol mass, efflux, and esterification, and on cellular cholesteryl ester (CE) hydrolysis using the mouse macrophage P388D1 cell line was investigated. HDL₂ at low concentrations (40 μg protein/ml) decreased CE content without affecting cellular free cholesterol content (FC), CE hydrolysis, or cholesterol biosynthesis. In addition, HDL₂ at low concentrations reduced cellular acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and increased FC efflux from macrophages. Thus, HDL₂ has two potential roles in reverse cholesterol transport. In one, HDL₂ is an acceptor of macrophage FC. In the other, more novel role, HDL₂ increases the availability of macrophage FC through the inhibition of ACAT. Elucidation of the mechanism by which HDL₂ inhibits ACAT could identify new therapeutic targets that enhance the transfer of cholesterol from macrophages to the liver.     

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

Increased or decreased hepatic lipase (HL) activity has been associated with coronary artery disease (CAD). This is consistent with the findings that gene variants that influence HL activity were associated with increased CAD risk in some population studies but not in others. In this review, we will explain the conditions that influence the effects of HL on CAD. Increased HL is associated with smaller and denser LDL (sdLDL) and HDL (HDL₃) particles, while decreased HL is associated with larger and more buoyant LDL and HDL particles. The effect of HL activity on CAD risk is dependent on the underlying lipoprotein phenotype or disorder. Central obesity with hypertriglyceridemia (HTG) is associated with high HL activity that leads to the formation of sdLDL that is pro-atherogenic. In the absence of HTG, where large buoyant cholesteryl ester-enriched LDL is prominent, elevation of HL does not raise the risk for CAD. In HTG patients, drug therapy that decreases HL activity selectively decreases sdLDL particles, an anti-atherogenic effect. Drug therapy that raises HDL₂ cholesterol has not decreased the risk for CAD. In trials where inhibition of cholesterol ester transfer protein (CETP) or HL occurs, the increase in HDL₂ most likely is due to inhibition of catabolism of HDL₂ and impairment of reverse cholesterol transport (RCT). In patients with isolated hypercholesterolemia, but with normal triglyceride levels and big-buoyant LDL particles, an increase in HL activity is beneficial; possibly because it increases RCT. Drugs that lower HL activity might decrease the risk for CAD only in hypertriglyceridemic patients with sdLDL by selectively clearing sdLDL particles from plasma, which would override the potentially pro-atherogenic effect on RCT. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).     

On the metabolic function of heparin-releasable liver lipase

Intravenous administration of specific antibody against heparin-releasable liver lipase (liver lipase) induced a 75% inhibition of the enzyme activity $\text{in situ}$. Administration of the antibody resulted in an increase of high density lipoprotein (density range 1.050–1.13 g/ml; HDL₂) phospholipid levels (20% after 1 h; 54% after 4 h). Short-term (1 h) treatment with antibody had no significant effect on any of the other lipoprotein components. After long-term (4 h) treatment the free cholesterol level of HDL₂ and all components in the very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) fraction were elevated (1.5–2.0 fold). In the low density lipoprotein (LDL) fraction only the phospholipid level was affected (increased by 72%). All lipid components in the HDL₃ fraction were decreased by the antibody treatment, but this decrease was only statistically significant for the cholesterolesters. The rate of removal of iodine-labeled high density lipoprotein (HDL) and LDL from serum was not affected by the antibody treatment.These results suggest that liver lipase may promote phospholipid removal $\text{in vivo}$ and show that a lowering of liver lipase $\text{in situ}$ has profound consequences for serum lipoprotein metabolism.     

High-performance aqueous gel permeation chromatography of serum lipoproteins: Selective detection of cholesterol by enzymatic reaction

A rapid method for the quantitation of cholesterol in each lipoprotein fraction has been developed which utilizes high-performance aqueous gel permeation chromatography followed by enzymatic reaction using reaction-type high-performance chromatography.Cholesterol in serum lipoproteins eluted from the column could be sensitively and selectively detected by the absorbance at 550 nm following the enzymatic reaction. The sensitivity of the detection for cholesterol measured by A₅₅₀ was compared with that for protein measured by A₂₅₀ using the standard lipoprotein fractions: low-density lipoprotein (LDL) and high-density lipoproteins (HDL₂ and HDL₃). The effects of changing the flow-rate and lengthening the column on the resolution of LDL and HDL were examined. Analyses of serum protein and cholesterol were performed with this method for human and animal subjects.     

Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals

The management of overweight subjects by interventions aimed at reducing inflammation is highly desirable. To date, observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity. However, direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking. Therefore, this study examined lycopene's ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects. Serum was collected before and after a 12-week intervention from 54 moderately overweight, middle-aged individuals. Subjects were randomised to one of three groups: control diet (< 10 mg lycopene/week), lycopene-rich diet (224–350 mg lycopene/week) and lycopene supplement (70 mg lycopene/week). HDL was subfractionated into HDL_2&3 by rapid ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum and HDL_2&3. Systemic and HDL-associated inflammation was assessed by measuring serum amyloid A (SAA) levels. HDL functionality was determined by monitoring the activities of paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT). Lycopene increased in serum and HDL_2&3 following both lycopene interventions (P<.001, for all), while SAA decreased in serum following the lycopene supplement and in HDL₃ following both lycopene interventions (P<.05 for all). PON-1 activity increased in serum and HDL_2&3 in both lycopene groups (P<.05, for all). Furthermore, the activity of CETP decreased in serum following the lycopene supplement, while the activity of LCAT increased in serum and HDL₃ following both lycopene interventions (P<.05 for all). These results demonstrate that in moderately overweight, middle-aged subjects, increasing lycopene intake leads to changes to HDL_2&3, which we suggest enhanced their antiatherogenic properties. Overall, these results show the heart-protective properties of increased lycopene intake.     

Effects of exercise cessation on lipids and lipoproteins in distance runners and power athletes

The purpose of this study was to determine the effects of short-term exercise cessation on lipid and lipoprotein profile and insulin sensitivity in highly trained runners (n=12; mean age 19.9 years) and power athletes (n=12; mean age 24.4 years). Following 14 days of exercise cessation, running time to exhaustion and maximal oxygen uptake decreased by 9.2% and 4.8% (P < 0.05) in the runners, while in the power athletes one repetition maximum squat and bench press did not change (P>0.05). No changes occurred in body composition. Data from a 2-h oral glucose tolerance test revealed an impairment of the glycemic state in all athletes (P<0.05). In contrast, exercise cessation did not significantly (P>0.05) alter plasma levels of cholesterol, triglycerides, and low density (LDL) and high density lipoprotein (HDL). No changes were observed in HDL₂, HDL_2b, and HDL₃ subfractions, LDL diameter, and qualitative LDL pattern (P>0.05). These data thus suggest that despite a decrease in insulin sensitivity, short-term exercise cessation, independent of exercise mode, was insufficient to alter plasma lipid and lipoprotein profiles in well-trained athletes.     

Location and motion of free cholesterol molecules in high density lipoprotein

Human high density lipoprotein (HDL₃) was reconstituted with the free cholesterol molecules replaced with 4-[¹³C]-cholesterol. 90 MHz [¹³C]-NMR spectra were obtained and two cholesterol resonances at chemical shifts of 41.73 and 42.20 ppm could be resolved. The former signal arises from the C-4 atom of cholesterol molecules associated with phospholipids and located in the surface of the HDL₃ particle while the latter resonance is due to cholesterol molecules associated with cholesterol ester and triglyceride molecules in the core. HDL₃ reconstituted without any cholesterol ester or triglyceride gave a single resonance at 41.73 ppm indicating that all the free cholesterol molecules are in the surface. 60% of the free cholesterol molecules present in normal HDL₃ are in the phospholipid monolayer around the surface where they undergo relatively restricted motion compared to the remaining 40% situated in the liquid core. The free cholesterol molecules can equilibrate between the two pools in the timescale 10ms–700s.     

Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R,C-108T,and L55M polymorphisms

BackgroundControversy exists regarding the role of the subfractions of high-density lipoproteins (HDL₂ and HDL₃) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL₃ and HDL₂ and its relationship with the polymorphisms mentioned, in a young population.MethodsThe polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry.ResultsThe results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL₃ subfractions was greater (62.83 ± 20 kU/L) than with HDL₂ (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL₃ and HDL₂.ConclusionsPON1 polymorphisms do not influence the HDL_-c, and the PON activity is greater in the HDL₃ than in the HDL₂, independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations.     

HDL Subspecies in Young Adult Twins: Heritability and Impact of Overweight

The association between abdominal obesity and atherogenic lipid profile emerges from complex interactions of genes and environment. We aimed to explore the heritability and effects of overweight on serum lipid profile (high‐density lipoprotein‐cholesterol (HDL‐C), HDL mean particle size, percentages of HDL_{2b, 2a, 3a, 3b, and 3c}, low‐density lipoprotein‐cholesterol (LDL‐C), LDL peak particle size and triglycerides (TGs)) in healthy, young adults. HDL‐C, LDL‐C, and TG were measured in 52 monozygotic (MZ) and 89 dizygotic (DZ) twin pairs, aged 23–32 years, chosen to represent a wide range of BMIs (17.6–42.9 kg/m²). Of them, 24 MZ and 26 DZ pairs were chosen at random for measurements of HDL mean and LDL peak particle sizes and percentages of HDL subspecies. The heritabilities of the lipid parameters adjusted for BMI were HDL‐C 73%, HDL mean particle size 56%, HDL subspecies 46–63%, LDL‐C 79%, LDL peak particle size 49%, and TG 64%. Genetic and environmental correlations between BMI and HDL‐C, LDL‐C, and TG were modest (0.3–0.4). Abdominal overweight (waist circumference ≥94 cm for males and ≥80 cm for females) associated with decreased HDL‐C, increased LDL‐C, and TG concentrations, smaller HDL mean particle size, lower HDL_2b, and higher HDL_3c percentages in both genders. Within MZ twins, controlling for genetic influences, within‐pair differences in HDL_3c percentage were associated with those in waist (r = 0.46, P = 0.032) and BMI (r = 0.51, P = 0.013). In conclusion, serum lipid parameters, including LDL peak and HDL mean particle sizes and HDL subspecies distribution are under strong genetic control. Overweight associated with significant lipid profile changes, particularly, small HDL_3c increased in overweight independent of genetic influences.