Normolipidemic Individuals Research Articles

Acute effect of moderate intensity physical exercise on postprandial hyperlipaemia of individuals with central obesity

Introduction: High postprandial triglyceride levels and obesity are associated with coronaropathy, and influence the pathogenesis and progression of atherosclerosis. Objective: To evaluate the effect of immediate acute physical exercise on postprandial hyperlipaemia in individuals with central obesity. Methods: Study included sedentary, normolipidemic individuals aged 18 - 30 years, with waist circumference >80 in for women and >94 for men. The physical exercise was performed for 45 minutes with 55% - 60% of the heart rate reserve. Triglyceride level tests were performed after fasting, and at time intervals of 1h and 3 h after lipid overload, a week before and immediately after a session of physical exercise. Results: Thirty-six individuals were evaluated (mean age 23.74 ± 4.05 years, 88.2% women, BMI = 28.4 ± 3.4). Fasting and post-prandial triglyceride levels were similar before and after the exercise (p = 0.87). A smaller rise in triglyceride levels was observed in the 1st hour in obese individuals (5%) compared with over-weight individuals (21%) p = 0.001. Conclusion: In individuals with central obesity, moderate intensity physical exercise performed immediately before lipid overload does not reduce the hyperlipidemic peak.

Relation of Increased Prebeta-1 High-Density Lipoprotein Levels to Risk of Coronary Heart Disease

Preβ-1 high-density lipoprotein (HDL) plays a key role in reverse cholesterol transport by promoting cholesterol efflux. Our aims were (1) to test previous associations between preβ-1 HDL and coronary heart disease (CHD) and (2) to investigate whether preβ-1 HDL levels also are associated with risk of myocardial infarction (MI). Plasma preβ-1 HDL was measured by an ultrafiltration-isotope dilution technique in 1,255 subjects recruited from the University of California-San Francisco Lipid and Cardiovascular Clinics and collaborating cardiologists. Preβ-1 HDL was significantly and positively associated with CHD and MI even after adjustment for established risk factors. Inclusion of preβ-1 HDL in a multivariable model for CHD led to a modest improvement in reclassification of subjects (net reclassification index 0.15, p = 0.01; integrated discrimination improvement 0.003, p = 0.2). In contrast, incorporation of preβ-1 HDL into a risk model of MI alone significantly improved reclassification of subjects (net reclassification index 0.21, p = 0.008; integrated discrimination improvement 0.01, p = 0.02), suggesting that preβ-1 HDL has more discriminatory power for MI than for CHD in our study population. In conclusion, these results confirm previous associations between preβ-1 HDL and CHD in a large well-characterized clinical cohort. Also, this is the first study in which preβ-1 HDL was identified as a novel and independent predictor of MI above and beyond traditional CHD risk factors.

Pistachios reduce LDL‐cholesterol when consumed as whole nuts as part of a controlled typical American diet in healthy normolipidemic individuals

Pistachios reduce LDL‐cholesterol when consumed as whole nuts as part of a controlled typical American diet in healthy normolipidemic individuals

Apolipoprotein E mRNA expression in mononuclear cells from normolipidemic and hypercholesterolemic individuals treated with atorvastatin

BackgroundApolipoprotein E (apoE) is a key component of the lipid metabolism. Polymorphisms at the apoE gene (APOE) have been associated with cardiovascular disease, lipid levels and lipid-lowering response to statins. We evaluated the effects on APOE expression of hypercholesterolemia, APOE ε2/ε3/ε4 genotypes and atorvastatin treatment in Brazilian individuals. The relationship of APOE genotypes and plasma lipids and atorvastatin response was also tested in this population.MethodsAPOE ε2/ε3/ε4 and plasma lipids were evaluated in 181 normolipidemic (NL) and 181 hypercholesterolemic (HC) subjects. HC individuals with indication for lowering-cholesterol treatment (n = 141) were treated with atorvastatin (10 mg/day/4-weeks). APOE genotypes and APOE mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by TaqMan real time PCR.ResultsHC had lower APOE expression than NL group (p < 0.05) and individuals with low APOE expression showed higher plasma total and LDL cholesterol and apoB, as well as higher apoAI (p < 0.05). Individuals carrying ε2 allele have reduced risk for hypercholesterolemia (OR: 0.27, 95% I.C.: 0.08-0.85, p < 0.05) and NL ε2 carriers had lower total and LDL cholesterol and apoB levels, and higher HDL cholesterol than non-carriers (p < 0.05). APOE genotypes did not affect APOE expression and atorvastatin response. Atorvastatin treatment do not modify APOE expression, however those individuals without LDL cholesterol goal achievement after atorvastatin treatment according to the IV Brazilian Guidelines for Dyslipidemia and Atherosclerosis Prevention had lower APOE expression than patients with desirable response after the treatment (p < 0.05).ConclusionsAPOE expression in PBMC is modulated by hypercholesterolemia and the APOE mRNA level regulates the plasma lipid profile. Moreover the expression profile is not modulated neither by atorvastatin nor APOE genotypes. In our population, APOE ε2 allele confers protection against hypercholesterolemia and a less atherogenic lipid profile. Moreover, low APOE expression after treatment of patients with poor response suggests a possible role of APOE level in atorvastatin response.

Morphology and structure of lipoproteins revealed by an optimized negative-staining protocol of electron microscopy

Plasma lipoprotein levels are predictors of risk for coronary artery disease. Lipoprotein structure-function relationships provide important clues that help identify the role of lipoproteins in cardiovascular disease. The compositional and conformational heterogeneity of lipoproteins are major barriers to the identification of their structures, as discovered using traditional approaches. Although electron microscopy (EM) is an alternative approach, conventional negative staining (NS) produces rouleau artifacts. In a previous study of apolipoprotein (apo)E4-containing reconstituted HDL (rHDL) particles, we optimized the NS method in a way that eliminated rouleaux. Here we report that phosphotungstic acid at high buffer salt concentrations plays a key role in rouleau formation. We also validate our protocol for analyzing the major plasma lipoprotein classes HDL, LDL, IDL, and VLDL, as well as homogeneously prepared apoA-I-containing rHDL. High-contrast EM images revealed morphology and detailed structures of lipoproteins, especially apoA-I-containing rHDL, that are amenable to three-dimensional reconstruction by single-particle analysis and electron tomography.

Apolipoprotein A5-1131T&gt;C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents

Apolipoprotein A5 (APOA5) and apolipoprotein E (APOE) play important roles in the metabolism of cholesterol and triglycerides. The aim of this study was to determine the allelic and genotypic distributions of the APOA5-1131T>C (rs 662799) and the APOE HhaI polymorphisms and to identify the association of both individual and combined APOA5-APOE genetic variants and the risk for dyslipidemia in children and adolescents. We genotyped 53 dyslipidemic and 77 normolipidemic individuals. The total cholesterol, triglycerides and HDL cholesterol were determined enzymatically. For APOA5 polymorphism, the presence of the allele C confers an individual risk for dyslipidemia (OR = 2.38, 95% CI = 1.15-4.89; P = 0.018). No significant differences were observed for lipid parameters among the APOA5 groups, except for a higher value of HDLc (P = 0.024) in C-carriers. The allelic and genotypic frequencies of APOE polymorphism were similar between groups and did not increase the susceptibility for dyslipidemia. None of the combined APOA5-APOE polymorphisms increased risk for dyslipidemia. We demonstrated an association between APOA5-1131T>C polymorphism and dyslipidemia in children and adolescents. This finding may be useful to guide new studies with genetic markers down a path toward a better characterization of the genetic risk factors for dyslipidemia and atherosclerotic diseases.

Intimal Smooth Muscle Cells

“Know the enemy and know yourself; in numerous battles you will never be in peril.” Sun Tzu ( The Art of War , Chapter III) The sixth-century BC Chinese military general Sun Tzu underscored the dangers of overconfidence in strategy. A similar view has been shared by other thinkers and applied further to various contexts other than the military. A major goal of the medical sciences is to develop effective, well-refined therapies. Accomplishing this task requires a comprehensive understanding of the biology of each component in the disease mechanism and realization of the limits of current knowledge. This view can apply not only to the development of new therapies but also to advanced diagnostics (eg, imaging and biomarkers). Article see p 2048 The biology of vascular smooth muscle cells (SMC) has been central to cardiovascular research. Many investigations have focused on the mechanisms of SMC accumulation in the tunica intima, an inner layer of the vessel wall between the endothelium and the media. Evidence suggests that, unlike arteries in other mammals, those in humans spontaneously develop intima of substantial thickness. In addition to higher cholesterol levels (even in normolipidemic individuals compared with other mammals) and other human-specific risk factors (eg, smoking), the intima may serve as a soil for the future development of atherosclerotic plaques.1 Coronary atherosclerosis leads to acute thrombotic complications, the leading cause of death in many countries. High plasticity represents a unique feature of SMC compared with other muscle cell types. A classic theory proposes that, on activation in response to injury or inflammatory stimuli, medial SMC migrate into the subendothelial space, proliferate, and produce extracellular matrix, forming the tunica intima. Once relocated to the intima, migrated SMC regain a quiescent phenotype over time.2,3 This phenomenon suggests that SMC can transiently modulate their phenotype, …

Apolipoprotein M expression increases the size of nascent preβ HDL formed by ATP binding cassette transporter A1

Apolipoprotein M (apoM) is a novel apolipoprotein that is reportedly necessary for pre beta HDL formation; however, its detailed function remains unknown. We investigated the biogenesis and properties of apoM and its effects on the initial steps of nascent pre beta HDL assembly by ABCA1 in HEK293 cells. Transiently transfected apoM was localized primarily in the endomembrane compartment. Pulse-chase analyses demonstrated that apoM is inefficiently secreted, relative to human serum albumin, and that approximately 50% remains membrane-associated after extraction with sodium carbonate, pH 11.5. To investigate the role of apoM in nascent pre beta HDL formation, ABCA1-expressing or control cells, transfected with empty vector, apoM, or C-terminal epitope-tagged apoM (apoM-C-FLAG), were incubated with (125)I-apoA-I for 24 h. Conditioned media were harvested and fractionated by fast-protein liquid chromatography (FPLC) to monitor HDL particle size. Pre beta HDL particles were formed effectively in the absence of apoM expression; however, increased apoM expression stimulated the formation of larger-sized nascent pre beta HDLs. Immunoprecipitation with anti-apoA-I antibody followed by apoM Western blot analysis revealed that little secreted apoM was physically associated with pre beta HDL. Our results suggest that apoM is an atypical secretory protein that is not necessary for ABCA1-dependent pre beta HDL formation but does stimulate the formation of larger-sized pre beta HDL. We propose that apoM may function catalytically at an intracellular site to transfer lipid onto pre beta HDL during or after their formation by ABCA1.

Plasma triglyceride levels and body mass index values are the most important determinants of preβ-1 HDL concentrations in patients with various types of primary dyslipidemia

ObjectiveExperimental studies have shown that the preβ-1 subclass of high-density lipoprotein particles (preβ-1 HDL) may play an important role in the reverse cholesterol transport pathway as the initial acceptors of cellular cholesterol. The aim of the present study was the direct comparison of preβ-1 HDL values in individuals with various types of primary dyslipidemias. MethodsFour hundred and eighty-six unrelated individuals were included in the study. According to their lipid values study participants were subdivided into four groups: control group (n=206), type IIA dyslipidemia group (n=148), type IIB dyslipidemia group (n=49) and type IV dyslipidemia group (n=83). ResultsAll dyslipidemic patients displayed higher concentrations of preβ-1 HDL compared to control individuals. However, patients with dyslipidemias characterized by an abnormal catabolism of triglyceride-rich lipoproteins (such as dyslipidemias of type IIB and IV) tend to have higher preβ-1 HDL values compared to patients with hypercholesterolemia, and this increase is proportional to the degree of hypertriglyceridemia. In addition, patients with metabolic syndrome exhibited significantly higher levels of preβ-1 HDL compared to individuals that do not fulfill the criteria for the diagnosis of this syndrome. Multiple regression analysis revealed that serum triglyceride concentrations and body mass index (BMI) values were the most important determinants of preβ-1 HDL levels in our population. ConclusionAll dyslipidemic patients exhibit increased preβ-1 HDL concentrations as compared to normolipidemic individuals. Whether this increase represents a defensive mechanism against atherosclerosis or it is indicative of impaired maturation of HDL particles and thus of a defective reverse cholesterol transport mechanism remains to be established.

Reactive oxygen species generation in peripheral blood monocytes and oxidized LDL are increased in hyperlipidemic patients

Objectives Experimental and in vitro evidences have established that reactive oxygen species (ROS) generated by vascular wall cells play a key role in atherogenesis. Here, we evaluated the rate of ROS generation by resting peripheral monocytes in naive hyperlipidemic subjects. Design and methods Primary hypercholesterolemic, combined hyperlipidemic, and normolipidemic individuals were studied. ROS generation and the mitochondrial electrical transmembrane potential were estimated by flow cytometry. Plasma oxidized (ox) LDL levels and lipid profile were measured by ELISA and enzymatic colorimetric methods. Results Both hyperlipidemic groups presented significantly higher rates of monocyte ROS generation and elevated plasma levels of ox-LDL. Combined hyperlipidemic subjects presented increased levels of small dense LDL and insulin. Significant positive correlations between monocyte ROS generation and ox-LDL concentrations were found in pooled data. Conclusions These data provide evidence that ROS production by circulating monocytes from hyperlipidemic subjects may contribute to the systemic oxidative stress and possibly to atherogenesis.

S-homocysteinylated LDL apolipoprotein B adversely affects human endothelial cells in vitro

ObjectiveIn recent years elevated homocysteine (Hcy) levels have been widely recognized as a risk factor for cardiovascular diseases (CVDs) and a connection between hyperhomocysteinemia and lipid metabolism has been suggested to have a possible role in endothelial vascular damage as lipoprotein fractions contain higher Hcy levels in hypercholesterolemia, compared to normolipidemic individuals. However, the biochemical events underlying the interaction between Hcy and LDL are still poorly understood. Methods and resultsHerein we have investigated the interaction of LDL with Hcy by measuring thiols S-linked to apoprotein using capillary electrophoresis and have evaluated the effect of S-homocysteinylated LDL on human endothelial cells (HECs). We found that Hcy binds to LDL in a dose dependent manner and the saturation binding is achieved at 100μmol/L Hcy in about 5h. Addition of Hcy resulted in a rapid displacement of other thiols bound to apoprotein and this was dependent on the concentration of Hcy added. For the first time we also demonstrated that treatment of HECs with homocysteine-S-LDL (Hcy-S-LDL) resulted in the induction of significantly higher levels of reactive oxygen species (ROS) compared to N-LDL (native LDL). Furthermore, the Hcy-S-LDL-induced a rise in intracellular ROS production was followed by a marked reduction of HECs proliferation and viability. ConclusionsAlthough the mechanism by which Hcy-S-LDL elicits the current cellular effects needs further investigation, our data suggest that intracellular ROS production induced by Hcy-S-LDL might be responsible for the observed HECs damage and indicate that Hcy-S-LDL may have some role in CVD.

Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux

Among the known mechanisms of reverse cholesterol transport (RCT), ATP binding cassette transporter G1 (ABCG1)-mediated free cholesterol (FC) transport is the most recent and least studied. Here, we have characterized the efficiencies of different acceptors using baby hamster kidney (BHK) cells transfected with human ABCG1 cDNA, which is inducible upon treatment with mifepristone. When normalized on particle number and particle surface area, the acceptor efficiency for FC efflux was as follows: small unilamellar vesicles (SUV)>LDL>reconstituted HDL>HDL2 = HDL3. Based on phospholipid content, the order was reversed. ABCG1 also mediated phospholipid efflux to human serum and HDL3. ABCG1-mediated FC efflux correlated significantly with a number of HDL subfractions and components in serum collected from 25 normolipidemic individuals: apolipoprotein A-II (apoA-II) (r2 = 0.7), apolipoprotein A-I (apoA-I) (r2 = 0.5), HDL-C (r2 = 0.4), HDL-PL (r2 = 0.4), α-2 HDL (r2 = 0.4), and preβ HDL (r2 = 0.2). ABCG1 did not enhance influx of FC or cholesteryl oleyl ether (COE) when cells were incubated with radiolabeled HDL3. ABCG1 expression did not increase the association of HDL3 with cells. Compared with control cells, ABCG1 expression significantly increased the FC pool available for efflux and the rate constant for efflux. In conclusion, composition and particle size determine the acceptor efficiency for ABCG1-mediated efflux. ABCG1 increases cell membrane FC pools and changes its rate of desorption into the aqueous phase without enhancing the association with the acceptor.

Periodontal Status in Subjects With Hyperlipidemia

Hyperlipidemia is a major risk factor for cardiovascular disease. Recent reports showed a possible association between periodontal disease and an increased risk for cardiovascular disease. The aim of this study was to evaluate whether hyperlipidemia has any influence on periodontal status. Fifty-one subjects with hyperlipidemia and 47 normolipidemic subjects participated in this study. Biochemical parameters, including plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels, and periodontal parameters, including plaque index (PI), probing depth (PD), clinical attachment level (CAL), and percentage of sites with bleeding on probing (BOP [%]), were evaluated. The mean values of PI, PD, CAL, and BOP (%) for the hyperlipidemic group were significantly higher than those for the control group. Plasma triglyceride, total cholesterol, and LDL-C levels were significantly and positively associated with PI, PD, BOP (%), and CAL. HDL-C was significantly, but negatively, associated with CAL. Plasma triglyceride level was significantly associated with PD and BOP (%) after further analyses. The results of our study showed that patients with mild or moderate hyperlipidemia manifested higher values of periodontal parameters compared to normolipidemic individuals. Further studies are needed to determine the effect of hyperlipidemia on periodontal disease.

Hyaluronan Accumulation Is Elevated in Cultures of Low Density Lipoprotein Receptor-deficient Cells and Is Altered by Manipulation of Cell Cholesterol Content

The extracellular matrix molecule hyaluronan (HA) accumulates in human atherosclerotic lesions. Yet the reasons for this accumulation have not been adequately addressed. Because abnormalities in lipid metabolism promote atherosclerosis, we have asked whether disrupted cholesterol homeostasis alters HA accumulation in low density lipoprotein receptor-deficient cell cultures. Cultured aortic smooth muscle cells (ASMC) from Watanabe heritable hyperlipidemic (WHHL) rabbits and skin fibroblasts from homozygous patients with familial hypercholesterolemia accumulated 2-4-fold more HA than corresponding cells from age- and sex-matched normolipidemic rabbits and individuals. This occurred in both cell-associated and secreted HA fractions and was independent of cell density or medium serum concentration. WHHL ASMC cultures synthesized twice the proportion of high molecular mass HA (>2x10(6) Da) as normal rabbit ASMC but showed a lower capacity to degrade exogenous [3H]HA. Most importantly, cholesterol depletion or blocking cholesterol synthesis markedly reduced HA accumulation in WHHL ASMC cultures, whereas cholesterol replenishment or stimulation of cholesterol synthesis restored elevated HA levels. We conclude the following: 1) maintaining normal HA levels in cell cultures requires normal cell cholesterol homeostasis; 2) HA degradation may contribute to but is not the predominant mechanism to increase high molecular mass HA accumulation in low density lipoprotein receptor-deficient WHHL ASMC cultures; and 3) elevated accumulation of HA depends on cellular or membrane cholesterol content and, potentially, intact cholesterol-rich microdomains.

Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response

The proximal section of the 3' untranslated region (3'UTR) of LDL receptor (LDLR) mRNA contains important regulatory sequences that control the messenger stability and mediate the cholesterol-lowering drug berberine (BBR)-induced increase in LDLR mRNA half-life. In the present study, we examined whether single nucleotide polymorphisms (SNPs) within this region cause a predisposition to the development of coronary heart disease (CHD) and whether they affect the response to BBR treatment. Genomic DNAs were isolated from peripheral blood of a Chinese cohort of 103 normolipidemic subjects and 94 hyperlipidemic CHD patients. The 1.1-kb proximal fragment of LDLR mRNA 3'UTR was PCR-amplified and sequenced. Six SNPs were detected within this region. Among them, the presence of SNP1 and SNP6 in both study groups showed complete association (r2=1). The frequency of individual SNPs and genotypes did not differ between CHD patients and normolipidemic individuals. Allelic variations did not correlate with total and LDL-cholesterol levels. To examine the effects of genetic variations in 3'UTR on BBR treatment, entire 2.5-kb regions of 3'UTR from three common SNP haplotypes were cloned into a luciferase reporter and the reporter constructs were transfected into HepG2 cells. The expression of reporter genes carrying different haplotypes of LDLR 3'UTR was increased to a similar extent upon BBR treatment. Taken together, these findings suggest that the 3'UTR LDLR polymorphisms commonly found in the Chinese population do not cause a predisposition to the development of CHD, nor do they affect the plasma lipid levels or the cholesterol-lowering effect of BBR.

An association study of sodium-lithium countertransport activity with glutathione S transferase (GST) T1 and GST M1 null polymorphisms in Greek dyslipidaemic patients and controls

Previous genomic linkage studies have produced evidence linking sodium-lithium countertransport activity (Na/Li CT) with various chromosomal regions including loci harbouring glutathione S transferase (GST) genes. The aim of this study was to examine the putative association of erythrocyte Na/Li CT activity with GST T1 and M1 gene null polymorphisms. Na/Li CT activity was determined in erythrocytes isolated from 85 individuals, using a standard assay procedure employing atomic absorption spectroscopy. Genotyping of the GST T1 and GST M1 null polymorphisms was accomplished with a multiplex PCR method. A general linear model using age, sex, smoking, dyslipidaemia and hypertension as covariates was used to examine the association of Na/Li CT activity with the GST T1 and GST M1 genotypes. Individuals with the GST T1 null genotype displayed marginally significantly (p=0.049) lower values of Na/Li CT activity compared to those harbouring at least one copy of the GST T1 gene. The significance of this association was eliminated following adjustment for covariates (p=0.150), but survived as a trend when the sample was limited to normotensive and normolipidaemic individuals (p=0.070). No association was detected between the GST M1 null polymorphism and Na/Li CT activity. The suggestive association of the GST T1 null polymorphism with erythrocyte Na/Li CT activity is in line with previously published data from genetic linkage and biochemical analyses and may be of potential prognostic value as regards the behaviour of the countertransport and the development of related pathologies under conditions of oxidative insult.

The roles of different pathways in the release of cholesterol from macrophages

Cholesterol efflux occurs by different pathways, including transport mediated by specific proteins. We determined the effect of enriching cells with free cholesterol (FC) on the release of FC to human serum. Loading Fu5AH cells with FC had no effect on fractional efflux, whereas enriching mouse peritoneal macrophages (MPMs) resulted in a doubling of fractional efflux. Efflux from cholesterol-normal MPM and Fu5AH cells to 15 human sera correlated well with HDL parameters. However, these relationships were reduced or lost with cholesterol-loaded MPMs. Using macrophages from scavenger receptor class B type I (SR-BI)-, ABCA1-, and ABCG1-knockout mice, together with inhibitors of SR-BI- and ABCA1-mediated efflux, we were able to quantitate efflux upon loading macrophages with excess cholesterol and to establish the contributions of the various efflux pathways in cholesterol-normal and -enriched cells. The removal of ABCA1 had essentially no effect on the total efflux when cell cholesterol levels were normal. However, in cholesterol-enriched cells, the removal of ABCA1 reduced efflux by 50%. Approximately 20% of the efflux stimulated by FC-loading MPM is attributable to ABCG1. The SR-BI contribution to efflux was small. Another pathway that is present in all cells is aqueous diffusion. Our studies demonstrate that this mechanism is one of the major contributors to efflux, particularly in cholesterol-normal cells.

CETP TaqIB polymorphisms and CETP activity in normolipidemic healthy northern Indians

Summary Background and aim Asian Indians have relatively lower high-density lipoprotein cholesterol (HDL-C) as compared to the other populations. Cholesterol ester transfer protein (CETP) is involved in the transfer of cholesterol esters from HDL-C to other lipoproteins in the plasma. In order to assess the role of CETP polymorphisms and their association with HDL-C, if any, we have studied the TaqIB polymorphism in intron 1 of CETP and its correlation with plasma lipids in 158 normolipidemic healthy subjects. Methods and results Plasma lipids levels were estimated using commercially available kits from Randox (India) and CETP TaqIB polymorphism were assayed by PCR-RFLP in 158 healthy normolipidemic individuals. The observed allelic frequencies of TaqIB polymorphisms, B1 and B2 were 43.0% and 56.9%, respectively. Lipid parameters were comparable between individuals with the different CETP TaqIB polymorphisms. The individuals categorized on the basis of their HDL-C levels ( 1.04 mmol/l), had comparable distribution of CETP genotypes. CETP activity was assessed in 84 of the total 158 individuals included in the study and did not vary among the CETP TaqIB genotypes. CETP activity in the females ( n = 39) negatively correlated with HDL-C levels. Conclusion This study reveals that CETP TaqIB polymorphisms are not associated with the decreased levels of HDL-C in healthy normolipidemic individuals. We are presently involved in studies to assess the precise role of CETP TaqIB polymorphism and CETP activity in hyperlipidemia in Asian Indians.

Green tea exerts antioxidant action in vitro and its consumption increases total serum antioxidant potential in normal and dyslipidemic subjects

Antioxidant defenses can be characterized as agents (enzymes and low-molecular-mass antioxidants) in biological systems that prevent the noxious action of free radicals or other reactive species. The present study examined whether the use of green tea may exert antioxidant action in vitro and improve antioxidant defenses and serum lipids in normal and dyslipidemic subjects. Forty-one hypercholesterolemic individuals, 18 women and 23 men (age [mean ± SD], 44.81 ± 14.41), were evaluated before and after the daily intake of 6 g of green tea in 500 mL of water for 1 month. Likewise, 27 normolipidemic individuals, 12 women and 15 men (age, 37.07 ± 16.08), were also evaluated. Serum lipids were measured by an automated clinical chemistry system. The total serum antioxidant potential (TRAP) and serum levels of lipid hydroperoxides were quantified using the chemiluminescence method. Total polyphenols present in green tea ingested by the patients were verified by using Folin-Ciocalteau reagent. The in vitro evaluation of green tea antioxidant activity was performed using microsomes obtained from rat liver, which was oxidized by tert-butyl hydroperoxide. From this system, thiobarbituric acid reactive substances were measured. In the in vitro test, green tea polyphenols proved to be efficient at protecting microsomes from the oxidant activity of tert-butyl hydroperoxide. There were no significant alterations in the lipid profiles of the normolipidemic or hypercholesterolemic subject groups. Although there was no decrease in lipid hydroperoxides, both groups showed increased antioxidant defenses, which was evidenced by TRAP. In conclusion, the results obtained indicate that besides achieving antioxidant action in vitro, the consumption of green tea increased the TRAP of normal and dyslipidemic subjects.

High‐density lipoprotein apolipoprotein A‐I kinetics: comparison of radioactive and stable isotope studies

To compare the kinetic determinants of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) concentration in lean normolipidaemic subjects using radioisotope and stable isotope studies. We pooled data from 16 radioisotope and 13 stable isotope studies to investigate the kinetics of apoA-I in lean normolipidemic individuals. We also examined the associations of HDL kinetic parameters with age, sex, body mass index (BMI) and concentrations of apoA-I, triglycerides, HDL cholesterol and low-density lipoprotein (LDL) cholesterol. Lean subjects from radioisotope and stable isotope studies were matched for age, gender, BMI and lipid profile. The apoA-I concentration was significantly lower in the radioisotope group than the stable isotope group (P = 0.031). There was no significant difference in HDL apoA-I fractional catabolic rate (FCR) and production rate (PR) between the groups. In the radioisotope group, HDL apoA-I FCR was significantly associated with apoA-I and HDL cholesterol concentrations (r = -0.681, P < 0.001 and r = -0.542, P < 0.001, respectively), whereas in the stable isotope group, only HDL apoA-I PR was significantly associated with apoA-I concentration (r = 0.455, P = 0.004). Our findings suggest that HDL apoA-I FCR is the primary determinant of apoA-I concentrations in lean subjects in studies using radiotracer techniques. By contrast, HDL apoA-I PR is the primary determinant of apoA-I concentration in lean subject in studies employing stable isotope methods. These discrepancies may be reconciled by differences in methodologies and/or study population characteristics.