Protein content and composition of human high density lipoprotein subfractions.

High density lipoprotein (HDL) was fractionated by ion exchange column chromatography using a continuous NaCl gradient of 0.06--0.13 M. It was found that, on the basic C apoprotein content, HDL is comprised of 3 subfractions. All 3 subfractions contain apo A-I and apo A-II but the apo A-I/apo A-II ratio is different in each subfraction and in the case of subfraction c, that fraction which eluted at highest NaCl concentrations, the A-I/A-II ratio varied even within this subfraction. Subfraction a contained no C apoprotein, subfraction b contained apo C-II and apo C-III-1 but no apo C-III-2 while subfraction c contained apo C-III-2 and trace amounts of apo C-II and C-III-1. Analysis of HDL2 and HDL3 shows that both contain all 3 lipoprotein subfractions, but in differing quantities.     

Hyperthyroidism influences the distribution and apolipoprotein A composition of the high density lipoproteins in man

Hyperthyroidism has a different influence on the major high density lipoprotein (HDL) components cholesterol, apoprotein (apo) A-I, and apo A-II. To characterize in greater detail the alterations induced by hyperthyroidism within the HDL subclasses, we investigated HDL distribution and composition in 11 hyperthyroid women before and during treatment. The plasma concentrations of total cholesterol, HDL cholesterol, phospholipids, apo A-I, and apo B were decreased when the patients were hyperthyroid compared with the values during treatment. Apo A-II and apo C-III levels were only slightly lower in the hyperthyroid state. Triglyceride and apo E concentrations did not change significantly during therapy. Analysis of lipoprotein subclasses separated by isopycnic ultracentrifugation revealed 1) marked decreases in low density lipoprotein (LDL) cholesterol, phospholipids, and apo B; 2) less pronounced reductions in the very low density lipoprotein (VLDL) lipid and apo B concentrations; and 3) a consistent decrease in the HDL2b (density, 1.063-1.100 g/ml) fraction in the hyperthyroid patients. The reduction in HDL2b mass was associated with lower concentrations of HDL2b cholesterol, phospholipids, and apo A-I. The HDL2b apo A-II levels remained constant during treatment. Hyperthyroidism, therefore, modified the apo A composition of the HDL2b particles and resulted in a decreased molar apo A-I to apo A-II ratio within HDL2b. Further analysis of HDL particles differing in their apo A composition; i.e. HDL particles containing apo A-I only [(A-I)HDL] or containing both apo A-I and A-II [(A-I + A-II)HDL], by immunological procedures suggested that hyperthyroidism influenced the apo A content of HDL2b mainly by changing the proportions of (A-I)HDL and (A-I + A-II)HDL and the amount of apo A-I associated with (A-I)HDL. Treatment reversed the preferential decrease in (A-I)HDL within the HDL2b subclass. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were similar in the untreated and treated patients. Consequently, the decreased mass of apo A-I and lipids within HDL2b in the hyperthyroid patients could be attributed to a reduced number of identically sized particles within this fraction. These data demonstrate that the thyroid hormones are important regulators of HDL metabolism through their influence on the concentration and distribution of apo A-I.     

Preliminary report: kinetic studies on the modulation of high-density lipoprotein, apolipoprotein, and subfraction metabolism by sex steroids in a postmenopausal woman

To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased. Simultaneous changes in post-heparin plasma hepatic triglyceride lipase activity paralleled those of LDL (and opposed those of HDL), decreasing with estrogen and increasing with stanozolol. During all three phases, autologous 125I-HDL turnover studies disclosed similarities between HDL2 and apolipoprotein A-I metabolism and between HDL3 and apolipoprotein A-II metabolism. In the untreated state the residence times of HDL2 and apo A-I were only half those of HDL3 and apo A-II. During estrogen treatment HDL2 and apo A-I, residence times were selectively prolonged, coming to resemble those of HDL3 and apo A-II, which remained unchanged. By contrast, during stanozolol treatment HDL3 and apo A-II residence times were selectively reduced, coming to resemble those of HDL2 and apo A-I, which remained unchanged. Apo A-I levels increased on estrogen and decreased on stanozolol, while apo A-II remained stable. Hence, estrogen increased HDL primarily by retarding the catabolism of the HDL2 subfraction rich in apo A-I, whereas stanozolol decreased HDL by accelerating the catabolism of HDL3, relatively rich in apo A-II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic effects of a biphasic oral contraceptive preparation containing ethinyloestradiol and desogestrel on serum lipoproteins and apolipoproteins

The effect of the administration of a biphasic oral contraceptive containing ethinyloestradiol and desogestrel on the distribution and composition of serum lipoproteins was studied in a group of 17 healthy female volunteers. The women were treated for a period of 6 months and compared with a control group of ten untreated volunteers. The serum lipoproteins were fractionated by density gradient ultracentrifugation into very low density lipoproteins (VLDL), low density lipoproteins (LDL), and into the high density lipoprotein (HDL) subfractions 2 and 3 (HDL2, HDL3). Lipids and apolipoproteins were assayed in the various fractions. No modification of either the lipid or apolipoprotein concentrations was observed in the control group. In the treated group, sex hormone-binding globulin (SHBG) and cortisol-binding globulin (CBG), and the serum content of cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) increased significantly after 3 and 6 months. The cholesterol and apolipoprotein B (apo B) content of VLDL increased significantly after 3 and 6 months, but remained unchanged in LDL. High density lipoprotein subfraction 2 (HDL2)-cholesterol was significantly increased after 3 and 6 months but apo A-I only after 6 months. Since apo A-II did not change, the apo A-I/A-II ratio increased significantly after 6 months of treatment. In the HDL3 fraction, the apo A-I increase was significant after 3 and 6 months, while the increase of apo A-II was significant after 6 months. The apo A-I/A-II ratio remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Separation of high density lipoprotein (HDL) using anti-apo A-I, apo A-II immuno-affinity chromatography to evaluate the effects of probucol]

An assessment has been made regarding the changes of the particles of lipoprotein A-I without A-II (Lp A-I) and lipoprotein A-I with A-II (LpA-I/A-II) which correspond to HDL subfraction isolated by the use of anti-apo A-I and A-II antibody affinity columns in order to quantitatively and qualitatively investigate the change of HDL caused by administration of probucol and pravastatin which are therapeutic drugs for hypercholesterolemia. Probucol caused significant decreases of HDL-cholesterol, plasma apo A-I/apo A-II ratio and particles larger in diameter than 10.4 nm. Comparing Lp A-I and A-I/A-II ratios with those in normolipidemic controls and the ratios before and after administration of probucol, the decrease of LpA-I ratio was found to be remarkable after prolonged administration of probucol, and it was presumed that the decrease of HDL cholesterol by prolonged administration reflects the decrease of LpA-I particles more than the decrease of LpA-I/A-II. On the other hand, no significant change was seen in HDL cholesterol, plasma apo A-I/apo A-II ratio or HDL particle size in the pravastatin group. It is considered essential to observe HDL from the aspect of apoprotein, which plays an important role in the metabolism of lipoprotein, in the assessment of the anti-atherogenic activity of HDL cholesterol in future. In other words, it is necessary to analyze the change of HDL from the aspect of Lp A-I and Lp A-I/AII and investigate their respective metabolisms and roles.     

High-density apolipoprotein A-I and A-II kinetics in relation to regional adiposity

High-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations decrease with increasing central adiposity. The present study investigated possible mechanisms for these effects by examining the relationship between body mass index, regional adiposity, and HDL apo A-I and A-II metabolism. Fifteen sedentary men and 10 male endurance athletes aged 22 to 44 served as subjects. HDL apo A-I and A-II metabolism was examined using 125I-labeled autologous HDL. Chest and thigh skinfold thickness and the ratio of chest to thigh skinfold thickness were used as indices of regional adiposity. The relationship of adiposity to HDL metabolism was examined using correlational and multiple regression analysis. In both subject groups, the fractional catabolic rate of apo A-I and A-II increased with increasing chest skinfold thickness and chest to thigh skinfold ratio (.43 < r2 < .66). This effect was partially independent of triglyceride or HDL cholesterol concentrations. Apo A-I and A-II fractional catabolic rates increased with increasing body mass index only in the sedentary men. Concentrations and synthetic rates (mg.d-1.kg-1) of apo A-I and A-II were not consistently related to body mass index or regional adiposity. Peripheral adiposity assessed by thigh skinfold thickness was not correlated with any parameter of apo metabolism. We conclude that HDL apo A-I and A-II catabolism increases with increasing central adiposity.     

Diverging effects of cholestyramine on apolipoprotein B and lipoprotein Lp(a). A dose-response study of the effects of cholestyramine in hypercholesterolaemia

Nineteen hypercholesterolaemic patients were randomly treated with either 16 or 8 g cholestyramine with a changeover after 6 weeks for a second 6-week period. During a third consecutive 6-week period all patients received 4 g cholestyramine daily. The low density lipoprotein (LDL) cholesterol and triglyceride concentrations decreased significantly (- 11%, - 21% and - 26% for LDL cholesterol on 4, 8 and 16 g, respectively) with a dose-response effect. However, the increase from 8 g to 16 g only caused a modest additional reduction of the lipid levels. The serum concentration of apolipoprotein (apo) B was correlated to the LDL cholesterol and decreased similarly in a dose-response fashion. However, the average reduction of apo B was less pronounced (- 4%, - 13% and - 17% on 4, 8 and 16 g of cholestyramine, respectively) resulting in a significant change of the apo B/LDL cholesterol ratio during treatment. There was a significant increase of the high density lipoprotein (HDL) cholesterol concentration, which was similar at all dose levels. Also, the apo A-I concentration in serum increased significantly but the relative decrease was less pronounced than that of HDL cholesterol, causing a significant decrease of the apo A-I/HDL cholesterol ratio. The apo A-II concentration in serum was unchanged or slightly decreased and the apo A-I/apo A-II ratio increased significantly.     

High density lipoprotein metabolism in endurance athletes and sedentary men

BACKGROUND. Endurance athletes have higher high density lipoprotein (HDL) concentrations than sedentary controls. To examine the mechanism for this effect, we compared HDL apoprotein metabolism in 10 endurance athletes aged 34 +/- 6 years (mean +/- SD) and 10 sedentary men aged 36 +/- 8 years. METHODS AND RESULTS. Subjects were maintained on controlled diets for 4 weeks, and metabolic studies using autologously labeled 125I HDL were performed during the final 2 weeks. Lipids and lipoproteins were measured daily during these 2 weeks, and the average of 14 values was used in the analysis. HDL cholesterol (58 +/- 14 versus 41 +/- 10 mg/dl), HDL2 cholesterol (26 +/- 10 versus 12 +/- 8 mg/dl), and apolipoprotein A-I (apo A-I) (144 +/- 18 versus 115 +/- 22 mg/dl) were higher in the athletes, whereas triglyceride concentrations (60 +/- 18 versus 110 +/- 48 mg/dl) were lower (p less than 0.01 for all). Postheparin lipoprotein lipase activity was not different, but hepatic triglyceride lipase activity was 27% lower (p less than 0.06) in the athletes. The athletes' mean clearance rate of triglycerides after an infusion of Travamulsion (1 ml/kg) was nearly twofold that of the inactive men (5.8 +/- 1.5 versus 3.2 +/- 0.9%/min, p less than 0.001). There was no differences in HDL apoprotein synthetic rates, whereas the catabolic rates of both apo A-I (0.15 +/- 0.02 versus 0.22 +/- 0.05 pools per day, p less than 0.01) and apolipoprotein A-II (apo A-II) (0.15 +/- 0.02 versus 0.20 +/- 0.04 pools per day, p less than 0.05) were reduced in the trained men. Apo A-I and apo A-II half-lives correlated with HDL cholesterol in each group (r greater than 0.76, p less than 0.05 for all) but not consistently with lipase activities or fat clearance rates. This relation between apoprotein catabolism and HDL cholesterol was strongest at HDL cholesterol concentrations of less than 60 mg/dl. CONCLUSIONS. We conclude that higher HDL levels in active men are associated with increased HDL protein survival. The mechanisms mediating this effect require better definition, and other factors appear to contribute to HDL cholesterol and protein concentrations among individual subjects.     

Serum lipoprotein lipid and apoprotein levels as indicators of the severity of angiographically assessed coronary artery disease

Serum lipoprotein cholesterol and triglycerides and apoproteins A-I, A-II and B were determined in 71 consecutive male subjects undergoing coronary angiography because of severe angina pectoris. Among the factors studied, apoprotein B, apoprotein B/A-I ratio, VLDL- and LDL cholesterol showed the most consistent association with the severity of coronary artery disease as assessed by angiography whereas serum HDL cholesterol and apoproteins A-I and A-II showed no correlation. Subjects with stenosis of the left main coronary artery had higher serum HDL cholesterol and apoprotein A-I and B levels than the others. In this series which comprised males with severe angina pectoris, derived from a population with high prevalence of coronary heart disease, LDL was the best indicator of the severity of coronary artery disease.     

Changes in the distribution and composition of high-density lipoproteins in primary hypothyroidism

The distribution and composition of high-density lipoprotein (HDL) subclasses were investigated in 14 women with severe hypothyroidism who were studied before and during treatment. The plasma concentrations of triglycerides, total cholesterol, HDL cholesterol, and of the apoproteins (apo) A-I, B, and E were increased in the hypothyroid state, while the apo A-II levels did not change significantly. After normalization of the thyroid function tests, the lipid and apoprotein levels were similar to those of normal individuals. Isopycnic ultracentrifugation in the density range 1.020 to 1.210 g/mL showed increases of both cholesterol and apo B in very-low-density lipoprotein (VLDL) and in low-density lipoprotein (LDL). The distribution of the HDL subclasses was modified in the hypothyroid subjects; both the less dense HDL fraction (d 1.063 to 1.100 g/mL; HDL2b), and the denser subclass (d 1.150 to 1.210 g/mL; HDL3b+3c) were increased, while the intermediate density subfraction (d 1.100 to 1.150 g/mL; HDL2a+3a) did not vary significantly. This redistribution of the HDL subfractions was associated with increased concentrations of cholesterol, phospholipid, and apo A-I in HDL2b, and of phospholipid and apo A-I in HDL3b+3c. Treatment of hypothyroidism decreased the concentrations of these fractions, and HDL2a+3a became the major HDL subclass in the euthyroid state. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were identical in the untreated and treated patients. The increased mass of protein and lipid within HDL2b and HDL3b+3c could therefore be attributed to an accumulation of identical-sized particles. The overall lipid and protein composition of the HDL lipoproteins was similar before and during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of the phenotypic expression of the A-IMilano apoprotein with plasma lipid and lipoprotein patterns

The plasma lipoprotein and apolipoprotein profile of 29 adult A-IMilano (A-IM) carriers and 29 age- and sex-matched non-affected subjects of the same kindred was examined, in order to investigate linkages between the lipid and apoprotein abnormalities and the phenotypic expression of the biochemical disorder. Carriers (A-IM+) showed a higher prevalence of hypertriglyceridemia (12 out of 29); they also had lower plasma total cholesterol, esterified cholesterol and phospholipids, compared to non-carriers. Lipoproteins were characterized by a significant enrichment of triglycerides in low and high density fractions (LDL and HDL), and by the expected striking reduction of HDL mass and cholesterolemia. Conversely, no significant alterations of the major circulating apolipoprotein levels, except for apo A-I and apo A-II, were noted in the A-IM+. The increased free cholesterol/esterified cholesterol ratio in plasma (most marked in HDL), was accompanied by a significant reduction of the lecithin cholesterol acyl transferase molar activity. Several correlations pertaining to lipids, lipoproteins and apoproteins were examined: cholesterol and triglycerides in HDL and, more remarkably, apoprotein A-I and C-III levels in plasma were significantly correlated in the A-IM+. While there was no significant prevalence of specific apo E phenotypes, plasma triglycerides and apo C-II levels were highly correlated in the carriers. The A-IM subjects, while in the presence of severe lipoprotein risk factors, may have alternative mechanisms of cholesterol disposal, potentially responsible for the apparently low prevalence of atherosclerosis.     

Decreased concentration of high density lipoprotein cholesterol in schizophrenic patients treated with phenothiazines

In chronic schizophrenic patients treated with phenothiazines (Chlorpromazine, Levomepromazine, Perphenazine) for long periods (average = 8 years), high density lipoprotein cholesterol (HDL-C) levels were significantly lower (P less than 0.001) compared with normal controls. The HDL subfractions showed that HDL3-C was significantly low (P less than 0.005) whereas HDL2-C was not. Both serum apo A-I and apo A-II levels were also low (P less than 0.005 and P less than 0.001, respectively) in schizophrenics treated with phenothiazines. The serum triglycerides (TG) level was significantly higher (P less than 0.05) in patients treated with phenothiazines than in controls. No significant differences in total cholesterol (TC), TG and HDL-C were found between users and nonusers of benzodiazepine in schizophrenic patients receiving phenothiazines. In addition to chronic schizophrenic patients, 8 new patients with schizophrenia and related diseases were studied. The serum HDL-C level decreased by 24% within 1 week following administration of phenothiazines. No significant differences were found in TC and TG levels for 10 weeks after initiation of phenothiazine administration.     

High density lipoprotein (HDL) subfractions in cardiovascular patients with low levels of HDL-cholesterol. Influence of hypertriglyceridaemia on subfraction concentration and composition

The major high density lipoprotein (HDL) subfractions were examined in angiographically defined cardiovascular patients with low HDL-cholesterol (HDL-C) levels. The aims were to study subfraction concentration and composition, and the extent to which hypertriglyceridaemia (HTG) modified these variables. Normotriglyceridaemic (NTG)-low HDL-C patients showed similar subfraction composition to age-matched healthy controls. However, these groups showed notable differences in subfraction composition compared to HTG-low HDL-C patients, particularly with regard to the HDL2 subfraction. HDL subfraction mass was significantly reduced in both cardiovascular groups; the HTG group showed a greater reduction in HDL2, whilst the NTG group showed a greater reduction in HDL3. The major HDL apoprotein (apo A-I) was lower in both subfractions of the cardiovascular patients. Apo A-II showed significant reductions only in the HTG patients.     

Mild exercise therapy increases serum high density lipoprotein2 cholesterol levels in patients with essential hypertension

In ten patients with essential hypertension who were on a prescribed regimen of supervised mild exercise, we examined serum lipids, HDL cholesterol subfractions (HDL2 and HDL3), and apolipoproteins. The findings were compared with data on age- and sex-matched hypertensives not on this regimen of exercise. Blood samples were obtained from the auricle during the multistage exercise test, and changes in levels of lactate were measured. The exercise was done for 30 minutes three times weekly for 10 weeks. A significant reduction of both systolic and diastolic blood pressure was evident at 10 weeks. Serum concentrations of HDL2 cholesterol increased significantly at 10 weeks, but there were no changes in total and HDL3 cholesterol. No significant changes were observed in serum concentrations of total cholesterol, triglyceride, and apolipoproteins, (apo) A-I, apo A-II, apo B, apo C-II, apo C-III and apo E following 10 weeks of exercise therapy. In the hypertensive controls who were not on exercise therapy, blood pressure as well as all parameters related to lipoproteins remained unchanged. Thus, mild exercise lowers blood pressure and improves the lipoprotein profile.     

Correlation of high density lipoprotein (HDL)-associated sphingosine 1-phosphate with serum levels of HDL-cholesterol and apolipoproteins

BACKGROUND: Extracellular sphingosine 1-phosphate (S1P) has been shown to contribute to the action of high density lipoprotein (HDL) on endothelial and smooth muscle cells. We examined the relationship of lipoprotein-associated S1P concentrations with cholesterol (C) and apolipoprotein (apo) contents of lipoprotein and lipoprotein subfractions characterized by capillary isotachophoresis (cITP). METHODS: Blood samples were drawn from 16 volunteers. S1P concentrations were quantified by bioassay based on the ability of S1P to stimulate its receptor. cITP was performed using plasma that had been prestained with NBD-ceramide. RESULTS: In plasma, S1P was concentrated in HDL and associated with LDL at a much lower concentration. HDL-S1P was the major determinant of the plasma S1P concentration. HDL-S1P was strongly and positively (p<0.001) correlated with serum levels of HDL-C (r=0.82), apo A-I (r=0.91) and apo A-II (r=0.92). HDL-S1P was strongly and positively (p<0.01) correlated with the apo A-I- and apo A-I/apo A-II-containing cITP HDL subfractions [fast HDL-C (r=0.66) and intermediate HDL-C (r=0.80)], but was not significantly correlated with apo E-containing slow HDL, suggesting that S1P is associated with both apo A-I HDL and apo A-I/A-II HDL. LDL-S1P was positively correlated (p<0.01) with levels of LDL-C (r=0.65) and apo B (r=0.85). CONCLUSION: Lipoprotein-associated S1P was related to the lipoprotein composition of cholesterol and apolipoproteins, suggesting that extracellular S1P may play different roles depending on the particles with which it is associated.     

Apolipoprotein A-II,HDL metabolism and atherosclerosis

Apolipoprotein (Apo) A-I and apo A-II are the major apolipoproteins of HDL. It is clearly demonstrated that there are inverse relationships between HDL-cholesterol and apo A-I plasma levels and the risk of coronary heart disease (CHD) in the general population. On the other hand, it is still not clearly demonstrated whether apo A-II plasma levels are associated with CHD risk. A recent prospective epidemiological (PRIME) study suggests that Lp A-I (HDL containing apo A-I but not apo A-II) and Lp A-I:A-II (HDL containing apo A-I and apo A-II) were both reduced in survivors of myocardial infarction, suggesting that both particles are risk markers of CHD. Apo A-II and Lp A-I:A-II plasma levels should be rather related to apo A-II production rate than to apo A-II catabolism. Mice transgenic for both human apo A-I and apo A-II are less protected against atherosclerosis development than mice transgenic for human apo A-I only, but the results of the effects of trangenesis of human apo A-II (in the absence of a co-transgenesis of human apo A-I) are controversial. It is highly suggested that HDL reduce CHD risk by promoting the transfer of peripherical free cholesterol to the liver through the so-called 'reverse cholesterol transfer'. Apo A-II modulates different steps of HDL metabolism and therefore probably alters reverse cholesterol transport. Nevertheless, some effects of apo A-II on intermediate HDL metabolism might improve reverse cholesterol transport and might reduce atherosclerosis development while some other effects might be deleterious. In different in vitro models of cell cultures, Lp A-I:A-II induce either a lower or a similar cellular cholesterol efflux (the first step of reverse cholesterol transport) than Lp A-I. Results depend on numerous factors such as cultured cell types and experimental conditions. Furthermore, the effects of apo A-II on HDL metabolism, beyond cellular cholesterol efflux, are also complex and controversial: apo A-II may inhibit lecithin-cholesterol acyltransferase (LCAT) (potential deleterious effect) and cholesteryl-ester-transfer protein (CETP) (potential beneficial effect) activities, but may increase the hepatic lipase (HL) activity (potential beneficial effect). Apo A-II may also inhibit the hepatic cholesteryl uptake from HDL (potential deleterious effect) probably through the SR-BI depending pathway. Therefore, in terms of atherogenesis, apo A-II alters the intermediate HDL metabolism in opposing ways by increasing (LCAT, SR-BI) or decreasing (HL, CETP) the atherogenicity of lipid metabolism. Effects of apo A-II on atherogenesis are controversial in humans and in transgenic animals and probably depend on the complex effects of apo A-II on these different intermediate metabolic steps which are in weak equilibrium with each other and which can be modified by both endogenous and environmental factors. It can be suggested that apo A-II is not a strong determinant of lipid metabolism, but is rather a modulator of reverse cholesterol transport.     

Is the ratio of apo B/apo A-I an early predictor of coronary atherosclerosis?

It is unknown which lipoprotein in childhood is the best predictor of atherosclerosis later on in life. We measured serum triglycerides, total cholesterol, its subfractions (LDL, HDL, HDL2, HDL3) and apoproteins (A-I, A-II, B) in two groups of children. They were offspring of fathers who had severe coronary atherosclerosis or no coronary sclerosis, as determined by coronary angiography. Fasting blood lipids were measured in 49 children of fathers with severe sclerosis, and in 37 children of fathers without sclerosis. Sons of fathers with severe coronary atherosclerosis had higher levels of apo B and of the ratio apo B/apo A-I than sons of fathers free of atherosclerosis. No differences in lipid levels in daughters were observed. These observations suggest that apolipoproteins play a part in early atherogenesis. They further indicate that it may be possible to detect children who have a high probability of developing severe coronary atherosclerosis later in life.     

Apolipoprotein A-I containing lipoproteins in coronary artery disease

At least 2 main types of lipoprotein particles are identified within HDL. Those which contain apo A-I and apo A-II (LpA-I:A-II) and those which contain apo A-I but not apo A-II (LpA-I). This study was designed to elucidate to what degree the HDL cholesterol decrease observed in coronary artery disease affects these 2 types of lipoprotein particles. Concentrations of LpA-I:A-II and LpA-I were measured in plasma from 100 normolipidemic male subjects with angiographically defined coronary artery disease (CAD(+)) or without CAD (CAD(-)) and from 50 control subjects, matched for age. CAD(+) subjects had significantly lower levels of HDL cholesterol, total apo A-I, and LpA-I than controls. When compared to CAD(-) subjects, only their levels of HDL cholesterol and LpA-I were found lower. In both cases (CAD(+) vs CAD(-) and CAD(+) vs controls), LpA-I levels were decreased while LpA-I:A-II levels were unchanged. Even, when the levels of their total plasma lipids and lipoproteins are normal, atherosclerotic patients are characterized by a different distribution of apo A-I between LpA-I and LpA-I:A-II. These data support the view that LpA-I might represent the "antiatherogenic" fraction of HDL.     

Relationship between plasma phospholipid transfer protein activity and HDL subclasses among patients with low HDL and cardiovascular disease

Low levels of high density lipoproteins (HDL) are associated with an increased risk for premature cardiovascular disease. The plasma phospholipid transfer protein (PLTP) is believed to play a critical role in lipoprotein metabolism and reverse cholesterol transport by remodeling HDL and facilitating the transport of lipid to the liver. Plasma contains two major HDL subclasses, those containing both apolipoproteins (apo) A-I and A-II, Lp(A-I, A-II), and those containing apo A-I but not A-II, Lp(A-I). To examine the potential relationships between PLTP and lipoproteins, plasma PLTP activity, lipoprotein lipids, HDL subclasses and plasma apolipoproteins were measured in 52 patients with documented cardiovascular disease and low HDL levels. Among the patients, plasma PLTP activity was highly correlated with the percentage of plasma apo A-I in Lp(A-I) (r=0.514, p<0.001) and with the apo A-I, phospholipid and cholesterol concentration of Lp(A-I) (r=0.499, 0.478, 0.457, respectively, p≤0.001). Plasma PLTP activity was also significantly correlated with plasma apo A-I (r=0.413, p=0.002), HDL cholesterol (r=0.308, p=0.026), and HDL₂ and HDL₃ cholesterol (r=0.284 and 0.276, respectively, p<0.05), but no significant correlation was observed with Lp(A-I, A-II), plasma cholesterol, triglycerides, or apo B, very low density lipoprotein cholesterol or low density lipoprotein cholesterol. These associations support the hypothesis that PLTP modulates plasma levels of Lp(A-I) particles without significantly affecting the levels of Lp(A-I, A-II) particles.