Plasma apolipoprotein concentrations in familial apolipoprotein A-I and A-II deficiency (Tangier disease)

Familial apolipoprotein A-I and A-II deficiency (Tangier disease) is characterized by cholesterol ester deposition in histiocytes, decreased plasma cholesterol and low density lipoprotein cholesterol (C-LDL), and a striking deficiency of high density lipoproteins (HDL). We measured plasma lipid, lipoprotein cholesterol, and plasma apolipoprotein (apo) A-I, A-II, B, C-I, C-II, C-III, D, and E concentrations in 7 Tangier homozygotes, 2 obligate heterozygotes, and 50 normal subjects. Heterozygotes had modest reductions in high density lipoprotein cholesterol (C-HDL), plasma apoA-I, and apoA-II levels. Mean concentrations (±SD) of plasma C-HDL and apolipoproteins A-I, A-II, B, C-I, C-II, C-III, D, and E in mg% in normals were: 50 ± 14, 134 ± 24, 68 ± 18, 98 ± 20, 7 ± 2, 3.7 ± 2, 13 ± 5, 10 ± 4, and 10 ± 4, respectively; and in homozygotes were: 1 ± 1, 1.3 ± 0.7, 4.8 ± 2.5, 82.6 ± 18, 4.1 ± 1.7, 2.3 ± 0.9, 6.5 ± 3.8, 2.2 ± 0.5, and 5.4 ± 3.1, respectively. Homozygotes had C-HDL, apoA-I and apoA-II levels which were 2%, 1%, and 7% (p < .001) of normal, respectively, and mean levels of apolipoproteins B, C-I, C-II, C-III, D, and E which were 84%, 59%, 62%, 50%, 22%, and 54% of normal, respectively. There was heterogeneity of these latter apolipoprotein concentrations among homozygotes. Mean apoC-I, apoC-III, apoD, and apoE levels were significantly less than normal (pp < .05) in homozygotes. These data indicate that homozygotes have variable but generally decreased apoC and apoE levels, a deficiency of apoD, and a striking reduction in plasma apoA-I and apoA-II concentrations.     

The effect of age, sex, alcohol consumption and cigarette smoking on serum concentrations of lipids and apolipoproteins in Zimbabwean blacks

Serum concentrations of total cholesterol, HDL cholesterol, triglycerides and apolipoproteins A-I and B were studied in black subjects with no known risk factor for coronary heart disease and in subjects with a single risk factor. The concentrations of lipids and apolipoproteins were sex-dependent. HDL cholesterol and apolipoprotein A-I were age-dependent in females (P less than 0.05 and P less than 0.01, respectively). There was a dose-related association between alcohol consumption and serum concentrations of triglycerides, HDL cholesterol, apolipoproteins A-I and B in males (P less than 0.001 and P less than 0.002, respectively in the heavy drinkers). The effects of cigarette smoking on the concentrations of serum lipids and apolipoproteins appear to be prominent in the heavy smoking subjects (P less than 0.001 and P less than 0.001, respectively). This work suggests that HDL cholesterol and apolipoprotein A-I may discriminate black subjects at risk of developing atherosclerosis.     

Effect of soybean crude fiber on the concentrations of serum lipids and apolipoproteins in hyperlipemic subjects

Effect of soybean crude fiber on the concentrations of serum lipids and apolipoproteins in hyperlipemic subjects was examined. The concentrations of serum triglycerides, VLDL triglycerides and VLDL cholesterol were decreased significantly following the administration of soybean crude fiber for 2 months. Neither were significant changes found in total cholesterol, LDL cholesterol, HDL cholesterol, apo A-I, apo A-II, apo C-II and apo B levels, nor in body weight before and after the administration of soybean crude fiber.     

Changes in serum apolipoprotein concentrations after L-thyroxine therapy in infants with congenital hypothyroidism

To further characterize the impact of thyroid hormones on the serum lipid profile, we studied serum apolipoproteins in infants with congenital hypothyroidism before and after L-thyroxine (L-T4) replacement therapy. Serum high-density lipoprotein cholesterol (HDLC) decreased after L-T4 therapy. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels did not change significantly after therapy. Two months after L-T4 replacement therapy, serum apolipoprotein A-I (apo A-I), C-III, and E declined and apo B increased significantly. No significant changes were observed for serum concentrations of apo A-II and C-II after L-T4 substitution. We conclude that in infants, thyroid hormone reduces serum levels of apo A-I, the principal protein component of HDLC, and this may contribute to the decline of serum HDLC concentrations after L-T4 replacement therapy.     

Promotion of sterol efflux and net transport by apolipoprotein E in lecithin: Cholesterol acyltransferase deficiency

In the plasma of 4 subjects homozygous for deficiency of lecithin:cholesterol acyltransferase, the level of many apolipoproteins (apo A-I, apo A-II, apo B, apo D) was greatly decreased relative to normal, while that of apo E is increased 5-fold. The lipoprotein complex containing lecithin:cholesterol acyltransferase with apo A-I and apo D in normal plasma is completely absent. The major part of apo E is unassociated with other apolipoproteins. The apoprotein-dependence of sterol efflux and net transport from human skin fibroblasts into plasma was determined by immunoaffinity chromatography. In normal plasma the major component of efflux of sterol radioactivity from labeled fibroblasts was dependent upon unassociated apo A-I. In LCAT-deficient plasma, apoprotein-dependent efflux was largely a function of unassociated apo E. When fibroblasts were incubated with fibrinogen-free unfractionated LCAT-deficient plasma, there was no spontaneous net transport of sterol either into or from the cells, indicating that efflux and influx rates were in balance. When apo E was removed by affinity chromatography, there was net transport from plasma to cells. These findings suggest a novel metabolic role for apo E in the promotion of sterol transport uncoupled to LCAT-activity.     

Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women

The associations of abdominal adiposity, fasting serum levels of insulin, and sex hormones with blood lipids, lipoproteins, and apolipoproteins A-I and B were studied cross-sectionally in 75 healthy, postmenopausal white women. In univariate analyses, abdominal adiposity (increased waist-to-hip girth ratio) and fasting insulin concentrations were negatively and significantly associated (P less than 0.05) with plasma high density lipoprotein cholesterol (r = -0.47 and -0.38, respectively) and apolipoprotein A-I (r = -0.37 and -0.36), and positively associated with log triglycerides (r = 0.54 and 0.33) and apolipoprotein B (r = 0.43 and 0.22). Sex hormone binding globulin was positively and significantly associated with high density lipoprotein cholesterol (r = 0.32) and negatively associated with log triglyceride (r = -0.45) and apolipoprotein B (r = -0.36). Estrone was positively and significantly associated with high density lipoprotein cholesterol (r = 0.27), apolipoprotein A-I (r = 0.23) and negatively associated with low density lipoprotein cholesterol (r = -0.24) and apolipoprotein B (r = -0.25). Total estradiol, free estradiol, free testosterone, and total testosterone were more weakly associated with the lipid measures. In multivariate analyses, abdominal adiposity remained significantly associated with high density lipoprotein cholesterol, log triglycerides, apolipoproteins A-I and B after adjustment for sex hormone binding globulin, estrone, and insulin concentrations. Insulin remained associated only with apolipoprotein A-I after adjustment for abdominal adiposity, estrone, and sex hormone binding globulin. Sex hormone binding globulin remained marginally associated with log triglyceride (P = 0.07) after adjustment for the remaining three factors. Estrone remained significantly associated with high density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.     

Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Plasma triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoproteins (apo) A-I, A-II, C-II, and C-III were determined and analyzed in 170 diabetic patients and 46 age-matched healthy normal subjects. The diabetics were separated into two groups: insulin-dependent diabetes mellitus (IDDM, n = 78) and noninsulin-dependent diabetes mellitus (NIDDM, n = 92). Significantly increased triglycerides, low HDL cholesterol, and normal cholesterol levels were found in the diabetics. The lipid profiles were similar in the IDDM and NIDDM groups. Plasma apo A-I, but not apo A-II, was low in both groups of diabetics. However, only in the IDDM subjects was there a statistically significant decrease in apo A-I when compared to normal subjects. The decreased apo A-I level negatively correlated with plasma triglycerides. Apo C-II and apo C-III were slightly increased in the diabetics compared to normal subjects. Apo C-II and apo C-III levels significantly correlated with plasma triglycerides (apo C-II, r = 0.70, P less than 0.0001; apo C-III, r = 0.71, P less than 0.0001). Only apo C-II correlated with total cholesterol. Thirty-eight to forty-two percent of the IDDM and NIDDM subjects had a clinical diagnosis of coronary artery disease (CAD) and/or peripheral arteriovascular disease (PAD). In the IDDM subjects, but not in the NIDDM subjects the incidence of CAD and/or PAD was associated with the decreased apo A-I levels as evaluated by a univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical studies on lipid metabolism in hyperthyroidism and hypothyroidism--evaluation of serum apolipoprotein levels before and after treatment

The present study was undertaken to assess lipid metabolism in patients with thyroid dysfunction with special reference to serum apolipoprotein levels. Serum lipid, lipoprotein and apolipoprotein levels were determined in 28 hyperthyroid and 16 hypothyroid female patients while untreated and euthyroid. Apolipoproteins were measured by the method of single radial immuno-diffusion (SRID). These results were compared with the values of 28 female controls. In the untreated hyperthyroid group, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were significantly decreased compared to the controls and increased after treatment. In hypothyroidism, these values before treatment were higher than those in the controls and decreased after treatment. Serum apo A-I, A-II, B and C-III levels were significantly decreased in the untreated hyperthyroid group compared to the control values. Apo C-II and E levels in hyperthyroidism were identical both before and after treatment compared with the control values, respectively. In the untreated hypothyroidism, apo B, C-II, C-III and E levels were significantly elevated compared to the controls, and these changes in apolipoproteins except apo C-II were restored after treatment. Apo A-I and A-II levels in the untreated hypothyroidism were not statistically different from the values after treatment or those in the control group. Serum thyroid hormone (T3, T4) levels inversely correlated apo B and C-III in all subjects. In hypothyroidism, serum TSH positively correlated with apo B, C-II and C-III. The increase in relative body weight (%RBW) in hyperthyroidism during treatment correlated with the changes of TC and LDL-C. In conclusion, these results indicate that thyroid hormones have a substantial influence on the serum apolipoprotein levels, and that measurement of apolipoproteins as well as lipids and lipoproteins in patients with thyroid dysfunction may be useful to evaluate the lipid metabolism and the effect of therapy.     

Reference values of plasma apolipoproteins A-I and B, and association with nonlipid risk factors in the populations of two Canadian provinces: Quebec and Saskatchewan. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To determine the population distribution of apolipoproteins A-I and B, and the relationship of apolipoprotein B to lipid risk factors for coronary artery disease. DESIGN: A stratified random sample of men and women aged 18 to 74 years selected from the provinces of Saskatchewan and Quebec in 1989 and 1990. OUTCOME MEASURES: Plasma concentrations of apolipoproteins A-I and B, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol and nonhigh density lipoprotein cholesterol for subjects who provided a fasting blood sample. MAIN RESULTS: Apolipoprotein B mean values increased with age from 0.80 g/L at age 18 to 24 years to a maximum of 1.16 g/L in the 45 to 54 year age group for men. For women, the values increased more gradually from 0.81 g/L for ages 18 to 24 to 1.19 g/L at ages 65 to 74 years. The distribution of apolipoprotein A-I was unrelated to age. Means for men varied from 1.35 g/L to 1.42 g/L and for women from 1.50 g/L to 1.61 g/L. Apolipoprotein B was strongly correlated with nonhigh density lipoprotein cholesterol (r2=0.89), and this was used to define apolipoprotein B concentrations less than 1.04 g/L as indicating low risk for coronary artery disease, from 1.04 g/L to less than 1.22 g/L as moderate risk, from 1.22 g/L to less than 1.40 g/L as high risk, and 1.40 g/L or greater as very high risk. The prevalence of high risk plasma apolipoprotein B levels was higher in men and women with triglycerides greater than 2.3 mmol/L. Apolipoprotein A-I was strongly correlated with high density lipoprotein cholesterol (r2=0.67), and this was use to identify apolipoprotein A-I concentrations of less than 1.20 g/L as a risk factor and 1.65 g/L or greater as an antirisk factor for coronary artery disease. The prevalence of apolipoprotein A-I of less than 1. 20 g/L was 19% in men and 6% in women, whereas the prevalence of apolipoprotein AI 1.65 g/L or greater was 9% in men and 28% in women. CONCLUSION: Reference values for plasma apolipoproteins A-I and B in a Canadian population random sample are given. Plasma apolipoprotein B and apolipoprotein A-I provide information that is complementary to that provided by low density lipoprotein and high density lipoprotein cholesterol levels.     

Alterations in rat serum lipids and apolipoproteins following clofibrate treatment

The in vivo effects of the hypolipidemic drug clofibrate (0.5 mmol/kg body wt daily p.o. for 7 days) on serum lipids and apolipoproteins have been studied in male rats. Clofibrate caused an increase in liver weight without affecting body weight. Triglyceride, total and free cholesterol and HDL cholesterol were decreased in sera of clofibrate-treated rats. The relative abundance, and accordingly the absolute quantities, of the polyunsaturated fatty acids linoleic (18:2), linolenic (18:3) and docosahexenoic (22:6) in serum triglyceride decreased in response to clofibrate treatment. The concentrations of serum apolipoproteins A-I, B and C-III were reduced in clofibrate-treated rats. The apolipoprotein E level was not altered. The distribution of apolipoproteins A-I, B, C-III and E between heparin-Mn supernatant and precipitate were unaffected. The unchanged C-III distribution indicates unaltered intravascular VLDL catabolism. Concurrent reductions in serum HDL cholesterol and ApoA-I in clofibrate-treated rats suggest a diminished production of lipoprotein particles containing ApoA-I. Reductions in serum ApoB and in the mass ratio of serum triglyceride to ApoB indicate a decrease in the number and size, respectively, of circulating triglyceride-rich lipoprotein particles. These observations suggest that the hypolipidemic effect of clofibrate in the normolipemic rat is caused mainly by diminished hepatic secretion, rather than by enhanced catabolism, of triglyceride-rich lipoproteins.     

Lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations were measured at 10 days and 4 months after myocardial infarction (MI) in 60 young Kuwaiti male MI survivors below the age of 40 years. Controls were matched for age, relative weights, smoking, dietary habits and physical activities. The young MI survivors had significantly higher levels of total and LDL-cholesterol, and ratios of LDL/HDL- and LDL/HDL2-cholesterol. Total VLDL and LDL triglycerides, and phospholipids were also elevated in MI survivors compared to controls. Similarly, plasma and LDL-apo B as well as the ratios of apo B/apo A-I were higher in the MI group. There was no significant change in the levels of VLDL and HDL3-cholesterol and of apo A-II in these patients compared to their controls. Concentrations of HDL- and HDL2-cholesterol and of plasma and HDL apo A-I were significantly lower in the young MI survivors compared to the control subjects. The better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2-cholesterol greater than apo B greater than apo A-I greater than VLDL-triglyceride greater than HDL-cholesterol greater than LDL/HDL2-cholesterol greater than triglycerides. The data indicate that measurement of HDL2-cholesterol, apo B and apo A-I may be useful indicators in assessing coronary artery disease risk than triglycerides (TG), total cholesterol (TC), LDL-cholesterol and HDL-cholesterol.     

Genetic and cultural inheritance of serum lipids, low and high density lipoprotein cholesterol and serum apolipoproteins A-I, A-II and B

The genetic and cultural heritability of serum cholesterol and triglyceride concentrations, as well as of the concentrations of low and high density lipoprotein cholesterol and serum apolipoproteins A-I, A-II and B, were estimated by path analysis in families selected through probands with premature myocardial infarction and in families randomly selected from the general population.

Genetic heritability was high for serum cholesterol (0.64) and low density lipoprotein cholesterol (0.67) concentrations, whereas it was lower for high density lipoprotein cholesterol level (0.42). Cultural inheritance was of less importance than genetic inheritance for all cholesterol variables. For serum triglyceride concentration genetic (0.33) and cultural (0.23) heritability was of similar significance. The results for serum apolipoproteins A-I and A-II parallelled those for HDL cholesterol. A marked intergenerational difference was found in the genetic heritability for apolipoprotein B concentration. The parental genetic heritability was 0.14, whereas the genetic heritability was 0.51 among siblings.     

Bile sequestrant therapy alters the compositions of low-density and high-density lipoproteins.

Bile sequestrant resins are used to lower the levels of low-density lipoprotein cholesterol in plasma because this may ameliorate atherosclerosis. Yet the levels and compositions of all the lipoproteins may affect atherogenesis. We have previously shown alterations in very-low-density lipoprotein (VLDL) metabolism in response to one of these agents, colestipol HCl. Here we report the effects of colestipol on the composition of low-density and high-density lipoproteins (HDL). Eighteen subjects with type II hyperlipoproteinemia were studied during baseline, diet, and drug periods lasting 2–3 mo. Lipoprotein lipids and apolipoproteins A-I, A-II, and B were measured, and indices of lipoprotein composition were calculated. Colestipol produced significant changes in all lipoproteins. VLDL-triglyceride rose transiently, the magnitude and duration both correlated with pretreatment values (r = 0.84 and 0.76, respectively, both p < 0.001). Low-density (density 1.006–1.063) lipoprotein cholesterol fell below the dietary mean by 28%, but low-density triglyceride fell by only 13% and apolipoprotein B by 17%. Thus, low-density lipoprotein cholesterol/apolipoprotein B ratios decreased (1.9 versus 1.6, p < 0.005). Low-density and very-low-density cholesterol/apoprotein B ratios also decreased significantly. Thus, all the apolipoprotein-B-containing lipoproteins had less cholesterol relative to apolipoprotein B. High-density lipoprotein cholesterol remained unchanged, although transient increases in high-density lipoprotein triglyceride occurred. Apolipoprotein A-I levels remained constant (∼105 mg/dl), but A-II levels fell (from 55 to 45 mg/dl); therefore, $\text{A-I}\text{A-II}$ ratios rose (2.0 versus 2.5, p < 0.001). Thus, alterations in the composition of both high-density and low-density lipoproteins occurred. Colestipol produced changes in lipoprotein composition that may have effects on atherogenesis independent of its effects on lowering plasma cholesterol. Further studies will be needed to determine whether or not these changes are beneficial.     

Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities

BACKGROUND: Hypopituitarism in adults is associated with increased vascular mortality, which has been attributed to GH deficiency. OBJECTIVE: To compare the lipid profile and coronary risk predicted by the Framingham Heart Study equation in GH-deficient hypopituitary patients and healthy age and gender-matched controls. DESIGN: A cross-sectional observational study. METHODS: We studied 50 adult-onset growth hormone deficient hypopituitary patients (23F, 27M), on appropriate conventional hormone replacement and 45 controls (22F, 23M) matched for age, gender and smoking habit. The subjects (age range 30-75 years) were free from diabetes, hypertension, ischaemic heart disease (IHD) and peripheral vascular disease. All hypogonadal male patients were on testosterone replacement therapy. A similar proportion of female patients (8/23) and controls (7/22) were on HRT. Body mass index (BMI), waist-hip ratio (WHR) and blood pressure were recorded. After an overnight fast blood glucose, total-cholesterol, triglycerides, HDL-cholesterol, apolipoproteins A-I, B and Lp (a) were measured. Coronary risk was calculated for each individual from age, gender, systolic blood pressure, total and HDL cholesterol, smoking habit and presence of diabetes and left ventricular hypertrophy using the Framingham equation. RESULTS: BMI and WHR were significantly increased in GHD hypopituitary adults of both sexes, but to a greater extent in females. Triglycerides were elevated in both sexes. Total and LDL-cholesterol were increased in both sexes (significantly only in males), and HDL cholesterol and apo A-I were lower (significantly only in females). The reduction in HDL cholesterol was correlated negatively with adiposity (BMI), particularly when centrally distributed (WHR) in patients and controls. LDL cholesterol did not correlate to adiposity but higher levels were present in GH-deficient subjects. The total to HDL cholesterol ratio was significantly increased in patients of both genders (P = 0.002). There were no differences in the apolipoproteins B and Lp(a) between patients and controls. Absolute risk (mean +/- SEM) of a fatal or non-fatal coronary event during the next 5 years was significantly greater in GHD hypopituitary patients than control subjects (4.82 +/- 0.73% vs. 2.94 +/- 0.53, P = 0.04). Cardiovascular risk relative to the local population (RR) was significantly higher in GHD hypopituitary adults (RR = 1.43 CL 1.06-1.80, P = 0.011) but not in the control group (1.08 CL 0.59-1.6). When divided by gender, RR for male patients was not increased (1.14 CL 0.83-1.45, P = 0.096). However, female patients had significantly higher RR (1.7 CL 1.05-2.5, P = 0.048). The RR for male and female controls was not different from the local population. CONCLUSION: Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.     

Lipoprotein distribution and composition in the human nephrotic syndrome

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.     

Clinical significance of measurements of serum apolipoprotein A-I, A-II and B in hypertriglyceridemic male patients with and without coronary artery disease

To examine the relationship of hypertriglyceridemia to coronary artery disease (CAD), we measured serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo) A-I, A-II and B in 82 male patients with angiographically defined CAD and 140 age-matched healthy controls. The CAD patients had significantly lower apo A-I and A-II and HDL-C levels, but had higher apo B and triglyceride levels than the controls. After adjustments of apolipoproteins for serum triglyceride, CAD patients had significantly higher apo B and lower apo A-I and A-II levels than the controls. Discriminant analysis showed that apo B was the best discriminator and that apo A-I was next. In the normotriglyceridemic subgroup HDL-C also had a sufficient power for discrimination between CAD patients and the controls, but in the hypertriglyceridemic subgroup HDL-C had no discriminative power. Both apo A-I and B had significant discriminative power between CAD patients and the controls, independently of the serum triglyceride level. These results indicate that measurements of serum apo A-I and apo B are useful for the study of coronary risk factor in hypertriglyceridemic subjects. Finally, it is necessary to sub-classify dyslipoproteinemia by serum apolipoprotein levels for predicting the future occurrence of CAD in the general population.     

Effects of insulin on hypercholesterolemia in the streptozotocin-induced diabetic rats fed a high cholesterol diet

The effect of dietary cholesterol (Ch) on plasma lipoprotein and apolipoproteins (apo) in diabetic rats was investigated. Ch-fed diabetic rats were severely hypercholesterolemic and hypertriglyceridemic. They had higher concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Concentration of high density lipoprotein (HDL) was decreased. beta-VLDL increased predominantly in Ch-fed diabetic rats, whereas IDL increased in the Ch and propylthiouracil-fed control rats. According to sodium dodecyl sulfate polyacrylamide gel electrophoresis, VLDL and IDL from Ch-fed diabetic rats were unusual in that they contained more apo E, A-I and A-IV. Concentrations of plasma apo A-I and apo E were measured by radioimmunoassay. The diabetic rats fed a labo chow showed a significantly lower concentration of plasma apo E than control rats. Plasma apo E was extremely higher in the diabetic rats fed a cholesterol diet. Plasma apo A-I was significantly increased in the diabetic rats fed a labo chow and those fed a cholesterol. Insulin treatment significantly decreased the concentrations of VLDL, IDL and LDL and plasma concentration and distribution of apolipoproteins in lipoprotein subfractions changed toward normal. However, decreased HDL in the Ch-fed diabetic rats was not recovered by insulin treatment.     

Role of apolipoproteins A-I, A-II and C-I in cholesterol efflux from endothelial and smooth muscle cells

The role of purified apolipoproteins A-I, A-II and C-fin theprocess of cholesterol efflux from cultured vascular endothelialand smooth muscle cells was studied [³H] Cholesterol pre-labelledcultures were exposed to serum-free medium supplemented withfree apolipoproteins or with apolipoproteins and phosphatidylcholineliposomes and the cholesterol efflux from the cells was determined.Free apolipoproteins A-I and A-II supported cholesterol effluxfrom vascular endothelial and smooth muscle cells to a higherextent than apolipoprotein C-I. The ability of free apolipoproteinsA-I and A-II to support cholesterol efflux was in correlationwith their specific binding to the cultures, while no specficbinding of apolipoprotein C-I was detected. The associationof apolipoprotein A-I with phosphatidylcholine liposomes resultedin a more than two-fold increase in cholesterol efflux comparedto free apolipoprotein A-I, while association of apolipoproteinsA-Il and C-I with phosphatidylcholine liposomes resulted ina very limited increase in cholesterol efflux above that achievedby the free apolipoproteins. These results suggest that apolipoprotein A-I is involved incholesterol efflux performed by high density lipoprotein. Furthermore,free apolipoproteins A-I and A-II, but not apolipoprotein C-Imay take an active part in cholesterol efflux from endothelialand smooth muscle cells.     

Apolipoproteins A-I and B as predictors of angiographically defined coronary artery disease

Apolipoprotein A-I and B concentrations were measured in 502 patients undergoing diagnostic cardiac catheterization to assess the predictive power of apolipoproteins B and A-I to discriminate between patients with coronary artery disease and those with normal coronary arteries as defined by coronary arteriography. The strength of the associations was compared with that of the associations between traditional risk factors (eg, smoking status, cholesterol levels) and coronary artery disease. The study population consisted of 154 women (mean age, 62.9 years) and 348 men (mean age, 59.6 years). The apolipoprotein A-I concentration averaged (+/- SD) 124 +/- 25 mg/dL and the apolipoprotein B concentration, 98 +/- 24 mg/dL. In all cases, the apolipoprotein measures showed a larger univariate difference between the "normal" (no coronary artery disease) group (66 patients) and the group with coronary artery disease (436 patients) than did the corresponding standard lipoprotein measures. The variable with the strongest association with coronary artery disease was the ratio of apolipoprotein A-I to apolipoprotein B, followed by apolipoprotein B level. These findings were confirmed using logistic regression, adjusting for other coronary artery disease risk factors. Fasting status did not affect apolipoprotein A-I or B concentrations. We conclude that the use of apolipoprotein A-I and B concentrations gives additional information to that supplied by lipoprotein measures to help predict the presence of coronary artery disease. Since traditional lipid measures may be changed by a meal, apolipoproteins A-I and B might be more useful measures when the fasting status of a patient is in question.