Serum Levels Of Apo Research Articles

Serum apolipoprotein A-I, A-II and B levels and their discriminative values in relatives of patients with coronary artery disease

Serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I, A-II and B concentrations were measured in 109 first-degree relatives of patients with angiographically defined coronary artery disease (CAD). Age- and sex-matched healthy factory employees were chosen as a control group. Male relatives of the CAD patients had significantly higher serum triglyceride and apoB levels, and significantly lower serum HDL-C and apoA-I levels than the controls. Female relatives of the CAD patients also showed similar differences in serum HDL-C, apoA-I and apoB levels. Discriminant analysis indicated that apolipoproteins were better discriminators than lipids in both patients with CAD and their relatives. In univariate analysis, the best discriminator was apoB between male relatives and the controls, and apoA-I between female relatives and the controls. The percentage of exact classification achieved using three variables (serum cholesterol, triglyceride and HDL-C) was 74% in male relatives and 70% in female relatives. By adding variables of apoA-I and apoB, the percentage of correctly classified subjects was increased to 82% and 80%, respectively. These results indicate that serum apolipoprotein abnormalities are prevalent in relatives of the CAD patients. These abnormalities may explain the familial aggregation of CAD.

Effect of dietary cholesterol on apolipoprotein E synthesis in the rabbit

Female New Zealand White rabbits were fed either rabbit chow or rabbit chow plus 1% (w/w) cholesterol for 14 days. The chow-fed rabbits had normal plasma lipoprotein profiles on agarose gel electrophoresis, 59 ± 5 mg of cholesterol and 5.5 ± 0.4 mg of apolipoprotein E (apoE) per dl of serum. The cholesterol-fed rabbits had significant amounts of β-VLDL in their serum, 1870 ± 140 mg of cholesterol and 96 ± 12 mg of apoE per dl of serum. Relative rates of apoE synthesis were determined by incubating hepatocytes in culture medium containing [ 3H]leucine for 15 min at 37°C and expressing the radioactivity incorporated into immunoprecipitable apoE as a percentage of the radioactivity incorporated into total protein. Hepatocytes from cholesterol-fed rabbits had twice the relative rate of apoE synthesis (1.05 ± 0.18%) of hepatocytes from chow-fed rabbits (0.55 ± 0.07%). This increase in synthesis could be a major contributor to the 17-fold increase in serum apoE levels in the cholesterol-fed rabbit.

High density lipoprotein and diabetes mellitus.

The serum HDL2-C, HDL3-C, apo AI and apo AII levels were measured in the non-insulin-dependent diabetic subjects (NIDD) and normal subjects to study the metabolism of HDL in the diabetics. The serum HDL2-C levels in the insulin-treated group were significantly higher than those in the normal group in which the total cholesterol (TC), triglyceride (TG), obesity index and age were matched whereas there was no difference between the serum HDL2-C levels in the oral agent-treated group or group treated by diet only and those in the normal group. These suggest that insulin increases the HDL2-C levels and the increase of the HDL2-C levels is not directly related to changes in the serum TC and TG levels, obesity index and age. No significant differences in the serum apo AI and apo AII levels were found between the insulin group and normal group. From these results it is suggested that in the insulin group the cholesterol/apoprotein ratio in the HDL2 is higher than that in the normal group. The serum apo AI and apo AII levels were significantly lower in the diabetics with an ischemic heart disease (IHD) than those in the diabetics without the IHD. The results show that in the diabetics the apo AI and apo AII play an important role in preventing the development of IHD.

Sex-related differences in the concentrations of apolipoprotein E in human blood plasma and plasma lipoproteins.

Apolipoprotein E (apoE) and lipoprotein cholesterol and triglycerides were measured in blood serum of 272 persons randomly selected from a large industrial population in northern California. Serum apoE level increased linearly by 0.013 mg/dl with each 1 mg/dl increase in very low density lipoprotein (VLDL) triglycerides. This estimate was independent of sex and the use of sex hormones by women. Compositional studies of isolated apoVLDL in 156 hypertriglyceridemic men and 162 normotriglyceridemic persons of both sexes from the same population also indicated that the content of apoE was independent of VLDL level, sex, and hormone use. The estimate of the relationship between serum apoE and VLDL-triglycerides derived from these compositional studies was comparable to that derived by regression analysis. Regression analysis also indicated that only 10-20% of the apoE in the serum of the average person is in the VLDL fraction. Serum apoE levels were 1.4 mg/dl higher in women than in men with the same VLDL-triglyceride level and 1.8 mg/dl lower in women using contraceptive drugs than in nonusers of like age and VLDL-triglyceride level.

Effects of Dietary Proteins on the Intestinal Synthesis and Transport of Cholesterol and Apolipoprotein A-I in Rats

Feeding a low-fat diet free of cholesterol to rats resulted in a low level of serum cholesterol and apolipoprotein A-I (apoA-I) when dietary protein was soybean protein as compared to casein. Since the small intestine is an important synthetic site for lipoproteins, the effects of dietary protein sources on the intestinal synthesis in vitro of cholesterol and apoA-I and the concentration of these components in the mesenteric lymph were studied. In rats fed a 1% fat diet, the apoA-I concentration in the lymph and the de novo synthesis of apoA-I in the small intestine segment were both low for animals fed a soybean protein diet as compared to a casein diet. The intestinal hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity was high in animals fed soybean protein, whereas the lymph cholesterol level was comparable. Even in rats fed a 5% fat diet, concentrations of serum cholesterol and apoA-I and lymphatic apoA-I were again significantly low for rats fed vegetable protein. These results indicate that the intestine plays an important role in the dietary protein-dependent regulation of serum cholesterol and apoA-I levels.

Radioimmunoassay of apolipoprotein a-ii.

A double antibody radioimmunoassay was developed for apolipoprotein A-II (apo A-II), one of the two major apoproteins of human high density lipoproteins (HDL). Apo A-II contains two identical polypeptide chains linked by a disulfide bond. A specific antiserum was raised in sheep. Tracer apo A-II was radiolabeled with 125I by the Bolton-Hunter technique. Reduction and carboxymethylation of apo A-II approximately doubled its immunoreactivity. Since normal sera were found to contain small amounts of monomeric apo A-II, this represented one potential source of error in the radioimmunoassay. Inclusion of 0.1 M sodium cholate in the assay system, however, led to identical immunoreactivity of dimeric apo A-II and the reduced and carboxymethylated protein. Radioimmunoassay using sheep anti-apo A-II detected 75% to 85% of the apo A-II contained in serum or HDL. Masked antigenic sites could be exposed by organic solvent extraction or, more simply, by dilution of serum samples in the buffer containing 0.1 M sodium cholate. Serum levels of apo A-II were measured in a population of consecutively and prospectively selected free-living subjects between 30 to 69 years of age. Levels were significantly (p less than 0.005) higher in females (n = 201; 42.0 +/- 10.3 mg/dl) than in males (n = 189; 39.0 +/- 8.4 mg/dl). Serum apo A-II levels correlated significantly with HDL-cholesterol levels but less strongly than apo A-I, the other major HDL apoprotein.

The quantitative determination of apolipoprotein A-I (apo-lp-Gln I) in human serum by radial immunodiffusion assay (RID)

A radial immunodiffusion (RID) assay was developed to determine the concentration of the major apolipoprotein (apolipoprotein A-I, apo-lp-GIn I) of human high density lipoproteins (HDL): 1. (1) In a random population sample of apparently healthy persons (104 women, 95 men) aged 40–49 years, serum levels of apo A-I were determined. For both women and men a value of 137 ± 23 mg/dl was found. 2. (2) Values of 139 ± 21 mg/dl were found in a group of 31 women taking oral contraceptives, i.e. an insignificant increase in apo A-I level. 3. (3) In two volunteers, apo A-I levels showed no significant variation in a 24-h period.

The intestine as a source of apolipoprotein A1.

The major apoprotein of rat mesenteric lymph chylomicrons has been isolated and characterized and shown to be identical to apoprotein A1 (apo A1) isolated from serum high density lipoprotein (HDL). During intestinal lipid absorption, active synthesis of apo A1 was demonstrated by radioactive amino acid incorporation into lymph chylomicron A1 as well as lymph HDL. Immunofluorescence studies of intestinal epithelium demonstrated a marked increase in apo A1 fluorescence, confirming an active synthesis of this apoprotein during lipid absorption. Quantitative immunoelectrophoretic methods were used to measure apo A1 in lymph and peripheral blood during various conditions designed to estimate the quantitative importance of intestinal apo A1 to the levels of circulating lipoproteins. During lipid feeding there was an increase in lymph apo A1 that was associated with lymph lipoproteins (50%) of density less than 1.006 g/ml whereas in basal lymph most apo A1 (85%) was in the lipoproteins of density greater than 1.006 g/ml. Lipid feeding in animals without lymph fistulas resulted in a significant increase in serum apo A1 levels; biliary diversion, designed to eliminate intestinal lipoproteins of density less than 1.006 g/ml, resulted in a significant decrease in serum apo A1 levels. These studies demonstrate that the intestine actively synthesizes apo A1 and is a significant source of this apoprotein for circulating lipoproteins.