High Density Lipoprotein Subfraction Distribution Research Articles

High density lipoprotein heterogeneity & function among Indians with coronary artery disease.

Impaired high density lipoprotein (HDL) functionality has been shown to be associated with cardiovascular disease risk. The study was aimed to identify the alterations in HDL function [antioxidative activity (AOA)] and subfraction distribution between acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) individuals and analysing the accuracy of HDL parameters to discriminate between the groups. HDL subfraction distribution analysis was performed in 200 coronary artery disease patients (ACS and SCAD) and 60 control individuals using dextran sulphate, heparin and manganese chloride precipitation method. In terms of HDL function, AOA was evaluated by dihydrorhodamine-based fluorescent cell-free assay and paraoxonase (PON1) enzyme paraoxonase and arylesterase activity. We found that higher AOA [odds ratio (95% confidence interval {CI})]: 0.09 (0.02-0.44), P<0.01 for SCAD; 0.008 (0.001-0.07), P<0.001 for ACS and higher PON1 activity [0.22 (0.8-0.59), P<0.01 for SCAD; 0.16 (0.06-0.4), P<0.001 for ACS] were associated with a lower odds of developing coronary artery disease (CAD). AOA of apoB-depleted serum was significantly correlated with HDL2-C/HDL3-C (HDL-cholesterol) ratio in controls (r=-0.31, P=0.01) and ACS (r=-0.18, P=0.04). It was observed that AOA and HDL subfraction distribution together could discriminate between the two groups of CAD with an accuracy of 72.8 per cent (P=0.004). Impaired AOA and altered subfraction distribution of HDL may be responsible for its diminished anti-athero protective activity and can discriminate between the two groups of CAD individuals.

Changes in serum afamin and vitamin E levels after selective LDL apheresis.

Afamin is a plasma vitamin E-binding glycoprotein partially associated with ApoA1-containing high-density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low-density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level. The serum level of afamin and oxidized LDL were measured by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments and in seven healthy controls. We also investigated the changes in total cholesterol, LDL-C, HDL-C, ApoB, ApoA1, HDL subfractions, and α- and γ-tocopherol levels during the treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α- and γ-tocopherol levels were detected by gas chromatography-mass spectrometry. The first treatment sessions decreased serum afamin levels by an average of 9.4%. Total cholesterol, LDL-C, HDL-C and ApoA1 levels decreased by 52.6; 61.8; 10.5; and 14.1%, respectively. We found that α- and γ-tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α- tocopherol/cholesterol and γ-tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Oxidized LDL levels significantly decreased. There was a shift toward the larger HDL subfractions. LDL apheresis moderately decreases the circulating levels of afamin parallel to lowering HDL-C and ApoA1 levels. Tocopherol levels decreases markedly compared to afamin levels, however, beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients.

High-density lipoprotein subfraction distribution correlates with plasminogen activator inhibitor-1 level in obesity

High-density lipoprotein subfraction distribution correlates with plasminogen activator inhibitor-1 level in obesity

Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia

Background and aimsSitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. MethodsSitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. ResultsEZE reduced (p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). ConclusionsEZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

Distribution of High-Density Lipoprotein Subfractions and Hypertensive Status: A Cross-Sectional Study.

The exact mechanisms of hypertension contributing to atherosclerosis have not been fully elucidated. Although multiple studies have clarified the association with low-density lipoprotein (LDL) subfractions, uncertainty remains about its relationship with high-density lipoprotein (HDL) subfractions. Therefore, we aimed to comprehensively determine the relationship between distribution of HDL subfractions and hypertensive status.A total of 953 consecutive subjects without previous lipid-lowering drug treatment were enrolled and were categorized based on hypertension history (with hypertension [n = 550] or without hypertension [n = 403]). Baseline clinical and laboratory data were collected. HDL separation was performed using the Lipoprint System.Plasma large HDL-cholesterol (HDL-C) and large HDL percentage were dramatically lower whereas the small HDL-C and small HDL percentage were higher in patients with hypertension (all P < 0.05). The antihypertensive drug therapy was not associated with large or small HDL subfractions (on treatment vs not on treatment, P > 0.05; combination vs single drug therapy, P > 0.05). However, the blood pressure well-controlled patients have significantly lower small HDL subfraction (P < 0.05). Moreover, large HDL-C and percentage were inversely whereas small HDL percentage was positively associated with incident hypertension after adjusting potential confounders (all P < 0.05). In the multivariate model conducted in patients with and without hypertension separately, the cardio-protective value of large HDL-C was disappeared in patients with hypertension (OR 95%CI: 1.011 [0.974-1.049]).The distribution of HDL subfractions is closely associated with hypertensive status and hypertension may potentially impact the cardio-protective value of large HDL subfraction.

High-density lipoprotein subfractions in relation with the severity of coronary artery disease: A Gensini score assessment.

The exact role of different high-density lipoprotein (HDL) subfractions in the pathogenesis of coronary artery disease (CAD) has not yet been fully explored. The aim of the present study was to examine the relationship between HDL subfractions and the severity of CAD in patients without statin therapy. A total of 382 consecutive patients (mean: 55.36 ± 11.30 years of age) who underwent coronary angiography from angina-like chest pain were investigated. Patients were classified into 2 groups according to the angiographic results: a CAD group (n = 283) and a control group (n = 99). The distribution of HDL subfractions was analyzed using a Quantimetrix Lipoprint HDL system. CAD severity was measured by Gensini score (GS). Compared with the control group, HDL-cholesterol (HDL-C), large HDL-C level, and the large HDL subfraction percentages in the CAD group were significantly lower (P = .002, P < .001, P < .001, respectively). Meanwhile, a small HDL-C level and the percentage of small HDL subfraction were significantly higher (P = .003, P < .001, respectively). Correlation analysis showed that the percentage of a large HDL subfraction was negatively correlated with GS (β = -0.191, P = .005), whereas the percentage of a small HDL subfraction positively correlated with GS (β = 0.145, P = .023) in patients with CAD. Small HDL subfraction was associated with the presence of CAD, whereas the percentage of large HDL and small HDL subfraction was negatively and positively associated with the severity of CAD, respectively.

Waist circumference is a strong and independent determinant of the distribution of HDL subfractions in overweight patients with cardiovascular risk factors

Our aim was to determine the influence of waist circumference on the repartition of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions in patients with increased waist perimeter and one or more cardiovascular risk factor. All 117 patients without lipid-lowering therapy underwent routine clinical, biological evaluation and isolation of the following lipid subfractions: HDL2b, HDL2a, HDL3a, HDL3b, HDL3c and LDL1, LDL2, LDL3, LDL4. Mean waist circumference was 102.9 cm for women and 109.4 cm for men, and 92 patients presented with metabolic syndrome. In the highest waist circumference tertile, when compared with the lowest one, an increased HDL3c (7.7% vs. 5.7% p=0.02) and a non-significant decrease of HDL2b percentages were observed with no difference in other subfractions. In multivariate analysis, only plasma triglycerides and waist circumference remained independent predictors of HDL3c percentage. In our population, waist circumference was a strong and independent determinant of a shift in the distribution of HDL toward denser particles.

Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity

Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (LDL); therefore, it may protect against atherosclerosis. Changes in the ratio of high-density lipoprotein (HDL) subfractions may alter the stability and the antioxidant capacity of PON1. The aim of the study was to examine the effect of atorvastatin treatment on the distribution of HDL subfractions, LDL size, cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and PON1 activity. In all, 33 patients with type IIa and IIb hypercholesterolemia were involved in the study. LDL sizes and HDL subfractions were determined by gradient gel electrophoresis. CETP, LCAT, and PON1 activities were measured spectrophotometrically. Three months of treatment with atorvastatin 20 mg daily significantly increased the HDL3 (+8.13%) and decreased the HDL2a and HDL2b subfractions (-1.57% and -6.55%, respectively). The mean LDL size was significantly increased (+3.29%). The level of oxidized LDL was significantly decreased (-46.0%). The PON1 activity was augmented by the atorvastatin treatment (+5.0%). The CETP activity positively correlated with the HDL2b level and negatively correlated with the HDL3 and HDL2a levels. Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity.

Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice

In low density lipoprotein receptor (LDLR)-deficient mice, overexpression of human plasma phospholipid transfer protein (PLTP) results in increased atherosclerosis. PLTP strongly decreases HDL levels and might alter the antiatherogenic properties of HDL particles. To study the potential interaction between human PLTP and apolipoprotein A-I (apoA-I), double transgenic animals (hPLTPtg/hApoAItg) were compared with hApoAItg mice. PLTP activity was increased 4.5-fold. Plasma total cholesterol and phospholipid were decreased. Average HDL size (analyzed by gel filtration) increased strongly, hPLTPtg/hApoAItg mice having very large, LDL-sized, HDL particles. Also, after density gradient ultracentrifugation, a substantial part of the apoA-I-containing lipoproteins in hPLTPtg/hApoAItg mice was found in the LDL density range. In cholesterol efflux studies from macrophages, HDL isolated from hPLTPtg/hApoAItg mice was less efficient than HDL isolated from hApoAItg mice. Furthermore, it was found that the largest subfraction of the HDL particles present in hPLTPtg/hApoAItg mice was markedly inferior as a cholesterol acceptor, as no labeled cholesterol was transferred to this fraction. In an LDLR-deficient background, the human PLTP-expressing mouse line showed a 2.2-fold increased atherosclerotic lesion area. These data demonstrate that the action of human PLTP in the presence of human apoA-I results in the formation of a dysfunctional HDL subfraction, which is less efficient in the uptake of cholesterol from cholesterol-laden macrophages.

Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity

Reduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4-30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 < or = absolute value of r < or = 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG- low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia.

Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery.

The morbidly obese have a disproportionately greater risk of hypertension, diabetes, and coronary artery disease than their lean or less seriously obese counterparts. Roux-en-Y gastric bypass surgery has been found to be highly effective in inducing, and sustaining, weight loss in individuals with morbid obesity. The purpose of the present study was to examine the effects of weight loss with Roux-en-Y gastric bypass surgery (GBP) on blood pressure, fasting blood glucose, and the lipid/lipoprotein status of 61 morbidly obese women and 21 men. Anthropometric and blood pressure assessments and blood samples for glucose and lipid/lipoprotein analyses were obtained before surgery and at 6 to 12 months postoperatively. By this time, morbidly obese (MO) males and females had lost 33% and 30% of their initial body weight, respectively, along with significant reductions in fasting blood glucose (p < 0.01) and systemic blood pressure (p < 0.05). Weight loss with GBP was also associated with significant reductions in the apoprotein B-containing lipoproteins and the triglyceride and cholesterol composition of these particles. There was a trend (p < 0.10) toward increased serum levels of high density lipoprotein (HDL)-cholesterol following GBP, and significant (p < 0.05) improvement in HDL subfraction distribution and composition. These findings demonstrate the effectiveness of GBP in inducing metabolic changes in the MO population, which may reduce the risk of coronary artery disease, diabetes, and hypertension.

Changes in plasma lipids and lipoproteins in humans during a 2-year period of dietary restriction in Biosphere 2.

A cohort study was performed of 8 people sealed inside Biosphere 2 to evaluate the effects of dietary restriction in humans on lipid and lipoprotein levels and the relationship of these levels to energy, fat, and protein content of the diet, and body weight, weight change, and energy expenditure. Eight healthy people aged 27 to 67 years, 4 women and 4 men, were sealed inside Biosphere 2 from September 26, 1991, to September 26, 1993, the longest sustained period in an "isolated confined environment" on record. They were studied throughout confinement and for more than 2 years after their exit and return to an ad libitum diet. Food available was severely restricted during most of the 2-year period inside Biosphere 2. High work output was maintained and food quality remained high, resulting in prolonged restriction of energy intake without malnutrition. Fasting plasma cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels; HDL subfraction distribution; dietary energy, fat, and protein content intake; and height, weight, weight change, and energy expenditure were measured. Total plasma cholesterol and triglyceride levels decreased 30% and 45%, respectively. The HDL and low-density lipoprotein levels also decreased and, in some participants, levels of HDL2 subfractions were increased. Multivariate analysis showed that the major cause of these changes was energy restriction. Energy restriction was the major factor leading to low lipid and lipoprotein levels. Energy restriction with adequate nutrition of young and middle-aged people may substantially reduce risk for atherosclerosis and consequent coronary artery and cerebrovascular disease.

Effects of short-term stanozolol administration on serum lipoproteins in hepatic lipase deficiency

We have identified a kindred in Providence, RI, deficient in hepatic triglyceride lipase (HL). The two affected brothers have coronary heart disease and elevated levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I. The lipoprotein lipase (LPL) activity is normal. We and others have postulated that the effects of oral anabolic steroids on HDL metabolism are mediated by HL. To test this hypothesis, we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL 2 cholesterol (90%), HDL 3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II. Although stanozolol failed to induce HL activity in the HL-deficient men, HDL cholesterol, HDL 2 cholesterol, and apo A-I were reduced a mean of 20%, 48%, and 32%, respectively. In contrast to controls, HDL 3 cholesterol (46%) and apo A-II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased LPL activity (124% ± 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% ± 3%, n = 3) in the three men with detectable levels. The data indicate that in addition to stimulation of HL activity, stanozolol treatment changes HDL cholesterol concentration and subfraction distribution by other mechanisms.

Age-related changes in lipid secretion of perfused livers from male Wistar rats donors.

Male Wistar rats show typical age-related variations in the distribution of high-density lipoprotein subfractions that include an increase in HDL1 and a decrease in HDL2 proportion. The role of liver in these variations was evaluated by studying the lipoprotein and bile secretions from perfused livers of 14 +/- 1 and 3.5 +/- 0.5 month old Wistar rats (adult and young animals, respectively). The lipid content of lipoproteins secreted from adult livers was higher in HDL2 fraction and lower in VLDL fraction. The lipid output did not show significant age-related variations in the case of HDL1 fraction. However, the lipoproteins secreted from adult livers contained a higher proportion of phospholipids, and a lower proportion of triacylglycerols in comparison with lipoproteins secreted by young livers. Therefore, the molar ratio of core to surface lipids was lower in lipoproteins secreted by adult livers. Adult livers showed a reduction in bile flow by about 37% with a significantly higher phospholipid secretion. These findings suggest that both the hepatic metabolism of glycerophospholipids and their repartition between plasma and bile compartments are affected by aging process. In conclusion, present data show that the age-related increase in plasma HDL1 proportion, previously observed in this rat strain in vivo, are not due to a higher liver secretion of these particles. Conversely, liver appears to have a major role in the age-related VLDL increase and in the variations of phospholipid lipoprotein secretion.

Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.

This study investigated in a healthy population (n = 220) the association of the TaqI B restriction fragment length polymorphism (RFLP) in the cholesteryl ester transfer protein (CETP) gene with plasma high-density lipoprotein (HDL) cholesterol concentration and subfraction distribution. A raised HDL cholesterol level was found in B2B2 homozygotes (B2 cutting site absent) and was associated specifically with a 45% increase in HDL2 compared with B1B1 homozygotes (B1B1, 77 +/- 39 mg/100 mL, mean +/- SD; B2B2, 112 +/- 59 mg/100 mL; P < 0.01). Total plasma, very-low-density lipoprotein, and HDL triglyceride levels did not differ among the genotype groups, nor did plasma apolipoprotein AI levels (B1B1, 1.45 +/- 0.35 mg/mL, mean +/- SD; B2B2, 1.56 +/- 0.33 mg/mL). Thus, the genetic variation appeared to be independent of metabolic factors that are known to regulate HDL levels. Plasma CETP exchange activity was unlikely to be the cause of the association, since it did not differ between genotype groups and was not correlated with HDL2 concentration. Multivariate analysis demonstrated that the TaqI B polymorphism had an effect on HDL cholesterol and HDL2 that was independent of age, sex, body mass index, oral contraceptive use, exercise, alcohol consumption, and plasma triglycerides. In smokers, the presence of the B2B2 genotype did not result in increased HDL cholesterol or HDL2, whereas in obese subjects, the difference between B1B1 and B2B2 individuals was diminished. We conclude that the TaqI B RFLP is associated with a quantitatively significant effect on plasma HDL2 levels that is independent of plasma triglycerides and interacts with lifestyle factors.

Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution

In a survey of a healthy population (n = 197), LDL cholesterol, plasma triglycerides and VLDL triglycerides were found to be substantially increased and plasma HDL cholesterol decreased in smokers. The lipid-associated atherogenic risk in smokers as assessed by the LDL/HDL ratio was significantly higher [2.89 (SD 1.18, n = 63)] than in non-smokers [2.38 (SD 0.98, n = 86) P < 0.01]. The lower HDL level found in smokers was explained by a lower HDL-2 subfraction as determined by analytical ultracentrifugation. HDL 2b, 2a and 3a, measured by gradient gel electrophoresis, were all lower in the smokers but this was only significant for HDL 2a. Smoking had no effect on Lp(a) levels. HDL cholesterol and HDL-2 were strongly negatively correlated whereas LDL cholesterol and LDL/HDL ratio were strongly positively correlated with the plasma triglyceride concentration. There was a small but significant reduction in plasma CETP activity [non-smokers 49% t/microliter (SD 17, n = 90), smokers 43% t/microliter (SD 17, n = 66) P < 0.05] but CETP activity was not correlated with any measure of HDL in this population. Smoking was found to be an important independent contributor to the variation in plasma triglyceride, HDL, HDL-2 and LDL/HDL ratio. After correcting for sex, age, BMI, alcohol consumption, oral contraceptive use and plasma triglycerides smoking was still found to be significantly associated with HDL and the LDL/HDL ratio. Upon adjustment for covariant factors the mean differences between smokers and non-smokers for HDL cholesterol, HDL-2 and LDL/HDL were 0.15 mM, 16 mg dl-1 and 0.39 respectively. There appeared to be important sex differences in the influence of smoking on plasma lipoproteins. In women the main impact of smoking was on triglyceride levels and they in turn affected LDL and HDL. In contrast, in men, smoking had little impact on triglycerides and affected HDL more directly. We conclude that smoking cigarettes has an important effect on plasma lipoprotein metabolism through multiple mechanisms.

The effect of gammalinolenic acid on the subfractions of plasma high density lipoprotein of the rabbit

The effect of dietary supplementation with evening primrose oil (containing 70% gammalinolenic acid) on the concentration of plasma lipids and lipoproteins of the New Zealand White rabbit was investigated. No significant changes were observed in the concentrations of plasma cholesterol or triglycerides during the treatment, although an increase in high density lipoprotein (HDL) cholesterol (P < 0.01) was observed at 4 weeks of evening primrose oil intake and 2 weeks after withdrawal. However, when HDL subpopulations were resolved by gradient gel electrophoresis, major alterations were observed in the distribution of HDL subfractions. These included an increase in HDL 2b (P < 0.001) and HDL 3c (P < 0.001) and the appearance of very large particles of HDL. These findings suggest that supplementation of diets with n-6 fatty acids may be effective in the long-term prevention of atherosclerosis.

Age and dietary polyunsaturated fat alter high density lipoprotein subfraction cholesterol concentrations in a pediatric population of African green monkeys.

African green monkeys were raised from birth to 60 months of age on diets containing cholesterol (0.8 mg/kcal) and enriched in polyunsaturated (polyunsaturated to saturated fat ratio [P:S] = 2.5) or saturated (P:S = 0.3) fat. Lipoproteins were isolated from plasma of a group of animals (N = 123) and were separated by gel filtration chromatography at 9, 14, 26, 38, and 50 months of age, which covered a period through adolescence into young adulthood. Total plasma cholesterol (TPC) concentrations were 16% lower (p = 0.01) in the polyunsaturated fat-fed group, and high density lipoprotein (HDL) cholesterol concentrations averaged 20% lower (p = 0.008) in this group between 14 and 50 months of age, while plasma apolipoprotein A-I (apo A-I) averaged 7% lower (p = 0.06) over this age interval in the animals. The HDL cholesterol to apo A-I ratio was found to be significantly lower (p = 0.006) in the animals fed the polyunsaturated fat diet. This suggested that the HDL subfraction distribution might differ between groups. In a subset of animals (n = 105, 64 male and 41 female), HDL was subfractionated by density gradient ultracentrifugation into six subfractions, HDL-I to HDL-VI, from lowest to highest density. The saturated fat-fed animals had significantly higher cholesterol concentrations in HDL-I and significantly lower cholesterol concentrations in HDL-III, HDL-IV, and HDL-V. These effects held across all ages studied; therefore, these diet effects were not age dependent. In both diet groups, the HDL subfraction pattern changed with age such that the HDL-I and HDL-II cholesterol concentrations decreased, and those of HDL-IV, HDL-V, and HDL-VI increased as the animals matured. The decrease in HDL-I with age appeared to result primarily from a decrease in HDL-I in males, while the HDL-I cholesterol concentration in females did not change with age. We conclude that diet, age, and gender all affect HDL subfraction distribution and therefore can potentially modify the relative atherogenicity of the plasma HDL populations. It remains for future studies to demonstrate the effectiveness of each subfraction in promoting or preventing the cholesterol deposition of atherosclerosis.

The distribution of high-density lipoprotein subfractions in coronary survivors

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Influence of serum triglycerides on the HDL pattern in normal subjects and patients with coronary artery disease

The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL 2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL 3 levels was found in any of the studied group. There was a clear negative correlation between HDL 2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL 3flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL 2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL 3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL 2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk.