Dusty Punch Cards and an Eternal Enigma: High-Density Lipoproteins and Atherosclerosis

Epidemiological, clinical, and experimental evidence has accumulated during the last decades suggesting that high-density lipoproteins (HDLs) may protect from atherosclerosis and its clinical consequences. However, more than 55 years after the first description of the link between HDL and heart attacks, many facets of the biochemistry, function, and clinical significance of HDL remain enigmatic. This applies particularly to the completely unexpected results that became available from some recent clinical trials of nicotinic acid and of inhibitors of cholesteryl ester transfer protein (CETP). The concept that raising HDL cholesterol by pharmacological means would decrease the risk of vascular disease has therefore been challenged

Moderate hyperalphalipoproteinaemia in a Brazilian population is related to lipoprotein lipase activity, apolipoprotein A-I concentration, age and body mass index

We investigated 95 Brazilian adults, aged 21-79 years, who were divided into two groups defined as having high-density lipoprotein (HDL)-cholesterol concentrations above [hyperalphalipoproteinaemia (HALP); n = 48] or below (controls; n = 47) the 90th percentile of a local population. The activities of lipid transfer proteins and enzymes involved in the plasma reverse cholesterol transport and the prevalence of factors that modulate HIDL metabolism (alcohol consumption, ponderosity, physical exercise, menopause and use of hormone replacement treatment in women and smoking) were measured, as well as the prevalence of cardiovascular disease and of its various risk factors. The two groups showed no differences in their frequencies of cardiovascular disease. The HDL2/H D L-3-cholesterol and triacylglycerol (triglyceride) ratios and the activities of the phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) were similar in both groups. Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were 35% higher (P=0.0002) and 40% lower (P=0.0006) respectively, in HALP compared with control subjects. In a multivariate analysis, HDL-cholesterol and its subfractions were influenced by LPL, apolipoprotein A-I, age (negative relationship) and body mass index (negative relationship). Use of alcohol and ponderosity, as well as the interaction of these factors, explained the LPL activity. HIL activity was modulated by smoking, and hormone-replacement therapy influenced the apolipoprotein A-I concentration. CETP activity was influenced by race and PLTP by age. The unique phenotype found in this Brazilian HALP population, namely low HIL and high LPL activities, could be determined mostly by genetic components, on which future work will focus.1061111

Smoking prevents the intravascular remodeling of high-density lipoprotein particles: Implications for reverse cholesterol transport

Smoking is a leading cause of atherosclerosis acting trough a wide spectrum of mechanisms, notably the increase of the proatherogenic effect of dyslipidemia. However, a severe atherosclerotic disease is frequently observed in smokers who do not present an overt dyslipidemia. In the present study, we sought to determine if abnormalities in lipid metabolism occur in normolipidemic smokers, focusing especially on the components of intravascular remodeling of high-density lipoprotein (HDL) For this purpose, we measured lipid transfer proteins and enzymes involved in the reverse cholesterol transport (RCT) system in 29 adults: 15 smokers and 14 controls. The blood samples were drawn in the fasting state, immediately after the smokers smoked 1 cigarette. The composition of HDL particles was analyzed after isolation of HDL fractions by microultracentrifugation. We observed that normolipidemic smokers present higher total plasma and HDL phospholipids (PL) (P < .05), 30% lower postheparin hepatic lipase (HL) activity (P < .01), and 40% lower phospholipid transfer protein (PLTP) activity (P < .01), as compared with nonsmokers. The plasma cholesteryl ester transfer protein (CETP) mass was 17% higher in smokers as compared with controls (P < .05), but the endogenous CETP activity corrected for plasma triglycerides (TG) was in fact 57% lower in smokers than in controls (P < .01). Lipid transfer inhibitor protein activity was also similar in both groups. In conclusion, the habit of smoking induces a severe impairment of many steps of the RCT system even in the absence of overt dyslipidemia. Such an adverse effect might favor the atherogenicity of smoking. (C) 2004 Elsevier Inc. All rights reserved.53785886

Acute in vivo chylomicron metabolism and postalimentary lipoprotein alterations in normolipidemic male smokers

Increased postprandial lipemia has been stated as one of the mechanisms responsible for atherogenesis in smokers. We measured the postalimentary lipid response and the in vivo intravascular delipidation index of an artificial chylomicron emulsion in healthy adult smokers and controls. The blood was collected in the fasting state immediately after the smokers smoked one cigarette. The lipemia was measured 2, 4, 6 and 8 h postalimentarily in smokers (S, n=8) and in non-smoking controls (C, n=8) and the chylomicron metabolism rate was measured 2, 4, 6, 8, 12, 16, 20, 24 and 30 min after the injection of an artificial emulsion to S (n= 10) and to C (n=10). The lipoproteins were isolated in the fasting period and 4 h after the fatty meal and their chemical composition in cholesterol, triglycerides, phospholipids and protein was determined. Smokers showed an increased lipolysis percentage value (mean +/-S.E.M) of the artificial chylomicron (39.1 +/-3.1) compared to controls (26.5 +/-3.3) and higher levels of HDL2-PL: 28.4 +/-4.3 (S) versus 16.2 +/-2.0 (C) mg/dl (mean +/-S.E.M.). In conclusion, the oral fat tolerance was not altered in smokers but an upregulation of the rate of metabolism of the TG-rich lipoproteins was elicited immediately after smoking one cigarette. (C) 2001 Elsevier Science B.V. All rights reserved.305416719910

Plasma 27-hydroxycholesterol/cholesterol ratio is increased in low high density lipoprotein-cholesterol healthy subjects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Sterol 27-hydroxylase converts cholesterol to 27-hydroxycholesterol (27-OHC) which is widely distributed among tissues and is expressed at high levels in the vascular endothelium and macrophages. There is a continuous flow of this oxysterol from the tissues into the liver; where it is converted to bile acids. Objective: Measure plasma concentrations of 27-OHC in subjects that differ according to their plasma HDL-C concentration. Methods: Healthy men presenting low HDL-C (1.55 mmol/L), n 18, BMI <30 kg/m(2) were recruited after excluding secondary causes that might interfere with their plasma lipid concentrations such as smoking, heavy drinking and diabetes. Blood samples were drawn after a 12 h fasting period for the measurement of 27-OHC by the combined GC/MS analysis utilizing deuterium-label internal standards. Results: The plasma ratio 27-OHC/total cholesterol (median and range nmoL/mmoL) was 50.41 (27.47-116.00) in the High HDL-C subjects and 6334 (36.46-91.18) in the Low HDL-C subjects (p = 0.0258). Conclusion: Our data indicate that the production of 27-0HC by extrahepatic tissues and its transport to the liver may represent an alternative pathway for a deficient reverse cholesterol transport system when plasma HDL-C is low. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.461516191621Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)LIMHC/FMUSP (Medical Investigation Laboratories, Hospital das Clinicas/Faculty of Medical Sciences of University of Sao Paulo)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2010/52654-6

Chemical modification of high density lipoprotein subfractions - HDL2 and HDL3 - after use of atorvastatin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Regardless of its effect on the concentrations of serum cholesterol, statins exert pleiotropic effects, including the regulation of endothelial function, reduced oxidative stress and inflammation, as well as a slight improvement in the concentrations of high density lipoprotein (HDL). However, its role on the composition of HDL is not yet established. The aim of this study was to evaluate the composition of HDL subfractions, HDL2 and HDL3, after 14 days of placebo and atorvastatin (10 mg/day) use in 30 asymptomatic volunteers. The serum parameters and the HDL subfractions compositions were determined using radiometric, nephelometric and biochemical enzymatic methods. We observed significant reductions of total cholesterol, low density lipoprotein (LDL) and apolipoprotein B-100 by 28%, 40% and 38%, respectively. The analyses of chemical composition of the subfractions revealed a lower lipid protein ratio in HDL2, suggesting enrichment in proteins, and also lower in HDL3, probably by an increase in the number of particles. Several mechanisms can be suggested for the effects observed after the use of atorvastatin, such as a possible action on the reverse cholesterol transport (decreased activity of hepatic lipase and increased phospholipid transfer protein, PLTP), which would explain the enrichment of HDL. The results suggest that statin use may be relevant in the primary prevention of atherosclerosis not only by its lowering effect on LDL-cholesterol and its anti-inflammatory effect but also by beneficial changes in HDL subfractions.524277283Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2006/60585-9]CNPq [471380/2008-3

Impact of Seasonality on the Prevalence of Dyslipidemia: A Large Population Study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Assessment of lipid profile parameters has been considered a cornerstone in classifying individuals and populations at risk for cardiovascular disease. Recently, however, preliminary data have raised the possibility of seasonal variations in these parameters, which may cause under- or overestimation. Biological rhythms and seasonal variation of lipid profile was investigated in 227 359 consecutive individuals who underwent health checkups in primary care centers between 2008 and 2010. Plasma low-density lipoprotein cholesterol (LDL-C) >130 mg/dL was 8% more prevalent during winter than summer, with a larger difference among women and middle-aged adults (p150 mg/dL were respectively 9% and 5% more prevalent during the summer (p<0.001). Variation amplitude was 3.4 +/- 0.3 mg/dL for HDL-C (p = 0.005), 7 +/- 2 mg/dL for LDL-C (p = 0.047), and 12 +/- 9 mg/dL for TG (p = 0.058). Based on a large population sample, this study confirms the existence of biological rhythms and seasonal variation in lipid profile. This finding must be particularly accounted for in cross-sectional analyses of relative risk, prevalence, or the rate of goal achievement for lipid parameters.30810111015Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq