Mean Apo Research Articles

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p<0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Metal-induced structural variability of mononuclear metal-binding sites from a database perspective

Metalloproteins are ubiquitous in all kingdoms of life. Their role and function are tightly related to the local structure of the metal-binding site. In this regard, the MetalPDB database is an invaluable tool since it stores the 3D structure of metal-binding sites and of their corresponding apo forms. In this work, we exploited MetalPDB to compute extensive statistics over >3000 clusters of mononuclear sites about the rearrangements occurring upon change in metalation state. For each cluster, we matched the holo and apo sites so that it was possible to average the distances between all possible pairs of Cα and donor atoms and thus quantitatively assess structural variations by computing the Δ values (mean apo distance – mean holo distance). For most of the structures the backbone is rigid with little to no rearrangement, while donor atoms experience significant changes of their relative position when the metal is removed. Sodium and potassium sites are an exception to this general observation. This is most likely caused by their preference for coordination by the main-chain oxygen atoms, making the rearrangement of donor atoms superimposable to that of the backbone. Magnesium and calcium show a different behavior, despite their chemical similarity: calcium sites undergo a larger reorganization upon metalation although both metals have similar percentage of backbone oxygen as donor atoms. We ascribe this observation to the structural and energetic factors regulating the selectivity for calcium over magnesium.

Defining apolipoprotein B treatment targets.

Apolipoprotein B (apo B) has been widely reported to be a better predictor of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). This is the reason apo B treatment target values based on the equivalence to LDL-C values in healthy population has been advocated using percentiles from population studies. The aim of this study was to determine the apo B values equivalent to currently used medical decision targets for LDL-C concentration in a population of healthy Nigerians and examine for any demographic influence. A total of 252 apparently healthy individuals (89 males, 163 females), between the ages of 30 and 65 years were selected from core health workers (medical and nursing staffs) of University College Hospital Ibadan between December 2015 and May 2016. Serum lipids and apo B were measured using enzymatic and immunoturbidimetry method, respectively. The mean apo B of the study population were 94 and 98 mg/dL in men and women, respectively. Mean apo B concentration was significantly higher in the female participants in the age groups above 55 years. LDL-C concentrations of 100, 130, 160, and 190 mg/dL corresponded to the 15th, 55th, 87th, and 95th percentile, respectively. The corresponding apo B concentrations were 73 mg/dL (15th percentile), 95 mg/dL (55th percentile), 124 mg/dL (87th percentile), and 145 mg/dL (95th percentile). The group of participants with LDL-C of <130 mg/dL and the group with equivalent apo B of <95 mg/dL has the same clinical and biochemical characteristics in both men and women. This study has defined apo B targets that may potentially be used to guide the initiation of therapy in persons with dyslipidemia. It has also demonstrated the population level relationship that exists between apo B and LDL-cholesterol and has shown the gender and age-related influence of apo B distribution in the population.

Evaluation of rice genotypes for seedling and reproductive stage drought tolerance

The present investigation was undertaken to evaluate 25 drought tolerant genotypes for seedling stage and reproductive stage drought tolerance. The genotypes were evaluated under gravimetric method at three moisture levels viz., i) control at 100% field capacity (FC) ii) water-deficit stress at 80% Field capacity (80% FC) and iii) water-deficit stress at 60% Field capacity (60% FC) for seedling stage drought tolerance. Observations were recorded on six morphological traits viz., seedling height, root length, shoot length, dry weight, leaf rolling and leaf drying and three physiological traits viz., chlorophyll stability index, proline content and nitrate reductase activity. The variety, APO and landraces viz., Kuliyadichan, Kattanur and Sivappuchithiraikar were identified with all desirable drought tolerant seedling traits and these genotypes also had high stress tolerance index (STI) for all the morphological traits. For reproductive stage drought tolerance, the moisture stress was imposed under field condition. Yield characters viz., number of days to maturity, panicle length, spikelet fertility and single plant yield and three physiological traits viz., chlorophyll stability index, proline content and nitrate reductase activity were recorded. Based on stress tolerance index (STI) and high mean performance, varieties viz., Anna (R) 4 and APO and landraces viz., Kattanur, Kuliyadichan and Sivappuchithiraikar were identified as drought tolerant lines for reproductive stage drought tolerance. From this study, APO, Kattanur, Kuliyadichan and Sivappuchithiraikar were identified as drought tolerant lines for seedling stage as well as reproductive stage. Therefore, these genotypes can be used as potential donors in the development of new drought tolerant varieties in rice.

Proteomic Serum Profile of Fatigued Men Receiving Localized External Beam Radiation Therapy for Non-Metastatic Prostate Cancer

ContextFatigue is the most distressing side effect of radiation therapy, and its progression etiology is unknown. ObjectivesThis study describes proteome changes from sera of fatigued men with non-metastatic prostate cancer receiving external beam radiation therapy (EBRT). MethodsFatigue scores, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue, and serum were collected from 12 subjects at baseline (before EBRT) and at midpoint (Day 21) of EBRT. Depleted sera from both time points were analyzed using two-dimensional difference gel electrophoresis, and up/down regulated proteins were identified using liquid chromatography-tandem mass spectrometry. Western blot analyses confirmed the protein changes observed. ResultsResults showed that apolipoprotein (Apo)A1, ApoE, and transthyretin (TTR) consistently changed from baseline (Day 0) to midpoint (Day 21). The mean ApoE level of subjects with high change in fatigue (HF: n = 9) increased significantly from baseline to midpoint and were higher than in subjects with no change in fatigue. The mean ApoA1 level was higher in HF subjects at baseline and at midpoint than in no fatigue subjects at both time points. The mean TTR level of no fatigue subjects was higher at baseline and midpoint than in HF subjects. ConclusionThese ApoE, ApoA1, and TTR results may assist in understanding pathways that can explain fatigue progression etiology in this clinical population.

Lipoproteins and the Development of Restenosis After Stent Implantation in the Superficial Femoral Artery in Patients with Peripheral Artery Disease

High levels of apolipoprotein B (apo B) are a risk factor for the development of major vascular events. We evaluated the association between plasma lipoproteins and the development of superficial femoral artery (SFA) in-stent restenosis and reocclusion in patients with peripheral artery disease. We included 139 patients with SFA stenting. Plasma lipoproteins were measured after stent implantation. Stent restenosis was assessed with duplex scan after 3, 6, and 12months. A stenosis grade was considered relevant if >50%. Seventy-two patients experienced recurrence of their atherosclerotic disease, meaning restenosis of >50% within 1year of follow-up. Ten of these patients had a stent occlusion. In the patients who experienced recurrence, the mean apo B level was 105.8 versus 94.9mg/dl in patients without recurrence (P<0.05). Patients without recurrence had higher high-density lipoprotein cholesterol levels than patients with recurrence (39.7 vs. 34.7mg/dl, P<0.05). Comparing patients with a stent occlusion (n=10) and those with a restenosis of 75-99% (n=28), the patients with a stent occlusion had higher levels of plasma cholesterol (234.1 vs. 185.9mg/dl, P<0.05), apo B (135.3 vs. 99.8mg/dl, P<0.05), low-density lipoprotein cholesterol (160.3 vs. 113.6mg/dl, P<0.05), and low-density lipoprotein apo B (115.5 vs. 82.4mg/dl, P<0.001) than the patients with restenosis of 75-99% (n=28). Changes in the lipid profile could be one reason for the development of restenosis and for the development of reocclusion after SFA stenting.

Rosiglitazone modifies HDL structure and increases HDL-apo AI synthesis and catabolic rates

Background Rosiglitazone is an agonist of the peroxisome proliferator-activated receptor (PPAR) gamma that may modify HDL metabolism in humans, but this effect has not been completely elucidated. Therefore, we determined the effect of rosiglitazone on apo AI turnover, HDL structure, and PON1 plasma activity. Methods Kinetic studies of HDL-apo AI radiolabeled with 125I were performed in 7 chow-fed, male, New Zealand white rabbits after 6 weeks of 0.32 mg/kg/d rosiglitazone-treatment vs. vehicle-treated rabbits ( n = 11). HDL size distribution was determined by polyacrylamide gradient electrophoresis and paraoxonase-1 (PON1); plasma activity was assessed spectrophotometrically using phenylacetate as substrate. Results Fractional catabolic rate (FCR) of HDL apo AI was higher in the rosiglitazone-treated group than in the control group (0.031 ± 0.004 vs. 0.025 ± 0.006 pools/h, respectively, p < 0.05). The mean apo AI production rate (PR) was 62% higher in the rosiglitazone group as compared to controls (0.918 ± 0.238 vs. 0.564 ± 0.160 mg/kg/h, p < 0.01). Accordingly, apo AI plasma levels in rosiglitazone-treated animals were about 37% higher than in the control group. Rosiglitazone-induced changes in apo AI turnover appeared concomitantly with a significant increase of phospholipids and a decrease in colesteryl esters content of the HDL. Compositional changes resulted in a relative increase of the HDL3b and HDL3c subfractions and a significant enhancement of the plasma PON1 activity (488.5 ± 138.2 vs. 595.2 ± 179.4 µmol/min/ml, p < 0.05). Conclusions Rosiglitazone increased apo AI plasma concentrations, resulting from an enhancement of apo AI synthesis, and induced the synthesis of smaller HDL particles with a concomitant increase of plasma PON1 activity. These modifications may contribute to the anti-atherogenic potential of rosiglitazone.

Correlating Cerebral Hypometabolism With Future Memory Decline in Subsequent Converters to Amnestic Pre–Mild Cognitive Impairment

Before symptomatic memory loss, healthy apolipoprotein E epsilon4 (APOE epsilon4) (OMIM 104310) carriers demonstrate accelerated longitudinal decline on memory tests, suggesting the existence of a transitional state between normal aging and mild cognitive impairment (MCI), which we have called amnestic pre-MCI. To support our neuropsychological construct of pre-MCI by characterizing and comparing the relationship between measurements of baseline regional hypometabolism and subsequent rates of memory decline in a group of individuals with neuropsychologically defined asymptomatic memory decline (pre-MCI group) and in nondecliners after controlling for APOE epsilon4 gene dose. Longitudinal study. Academic medical center. Of 139 healthy individuals in the Arizona APOE Cohort aged 50 to 69 years who underwent longitudinal neuropsychological testing and fludeoxyglucose F 18-positron emission tomography (FDG-PET) since 1994, 10 met our criteria for amnestic pre-MCI, and 15 showed no decline. Correlations between lower regional cerebral metabolic rates for glucose (CMRgl) and rates of verbal memory test decline that occurred at a mean of 41 months after baseline FDG-PET using an automated brain mapping algorithm (SPM5). The pre-MCI and nondecliner groups did not differ in mean (SD) age (56.8 [4.8] years), education (16.5 [2.3] years), sex (19 women [76%]), or APOE epsilon4 carrier status (12 epsilon4 carriers [48%)]. After controlling for APOE epsilon4 gene dose, the pre-MCI group had significant correlations between lower baseline CMRgl in the posterior cingulate, bilateral parietal, and left prefrontal regions (known to be preferentially affected by Alzheimer disease) and subsequent verbal memory decline. Nondecliners had significant correlations bilaterally in the posterior and midcingulate cortices. Correlations in the left parietal, left temporal, and bilateral frontal regions were significantly greater in the pre-MCI group than those in the nondecliner group. Individuals with amnestic pre-MCI showed significantly greater correlations between cerebral hypometabolism and subsequent long-term memory decline than nondecliners in Alzheimer disease-affected brain regions.

Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-β peptide levels in vivo

ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE) and exhibit increased amyloid load. To test whether excess ABCA1 protects from amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE abundance, demonstrating that this BAC supports modest ABCA1 overexpression in brain. However, this was observed only in animals that do not deposit amyloid. Comparison of ABCA1/APP/PS1 mice with APP/PS1 controls revealed no differences in levels of brain ABCA1 protein, amyloid, Abeta, or apoE, despite clear retention of ABCA1 overexpression in the livers of these animals. To further investigate ABCA1 expression in the amyloid-containing brain, we then compared ABCA1 mRNA and protein levels in young and aged cortex and cerebellum of APP/PS1 and ABCA1/APP/PS1 animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1 mice exhibited increased ABCA1 mRNA, but not protein, selectively in cortex. Additionally, ABCA1 mRNA levels were not increased before amyloid deposition but were induced only in the presence of extensive Abeta and amyloid levels. These data suggest that an induction of ABCA1 expression may be associated with late-stage Alzheimer's neuropathology.

Body composition, lipid and lipoprotein levels in childhood‐onset systemic lupus erythematosus

Objectives: Systemic inflammation, corticosteroid therapy, and reduced physical activity are risk factors for altered body composition in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess whether body composition differs between childhood‐onset SLE patients and healthy controls, and to investigate the impact of disease characteristics and lifestyle factors on body fat mass, serum lipids, and lipoproteins.Methods: Fat mass and lean tissue mass were measured in a cross‐sectional study of 68 childhood‐onset SLE patients and 68 matched healthy controls by dual‐energy X‐ray absorptiometry (DXA). The influence of disease, glucocorticosteroids, disease activity and severity, physical activity, and dietary intake on fat mass was evaluated by multiple linear regression analysis. Serum lipid and lipoprotein levels were measured.Results: Patients had a significantly higher fat mass [mean (SD) 35.3 (10.8) vs. 30.9 (11.1)%; p = 0.024] and lower lean mass [39.7 (9.8) vs. 44.4 (1.5) kg; p = 0.003] than controls. Corticosteroid use and the disease itself were significant independent predictors of greater fat mass, while disease activity, physical activity, and dietary intake had only a minor influence. Mean high density lipoprotein (HDL) cholesterol and apolipoprotein A1 (apo A1) levels were significantly lower (p<0.001), and the mean apo B/apo A1 ratio significantly higher (p = 0.004), in patients than in controls.Conclusion: Childhood‐onset SLE patients had a higher fat mass and lower lean mass than healthy controls and corticosteroid use was an independent predictor of increased fat mass. Patients had a more proatherogenic lipid profile, which will contribute to the increased risk of coronary heart disease in SLE patients.

Serum Apolipoprotein J in Health, Coronary Heart Disease and Type 2 Diabetes Mellitus

Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and is a component of high-density lipoproteins (HDLs). There is experimental evidence that it may be anti-atherogenic through its effects on cholesterol transport, smooth muscle cell proliferation and lipid peroxidation. HDLs containing apo J and apo A-I carry paraoxonase (PON1), which protects low-density lipoproteins from oxidative modification; however, the extent to which apo J affects coronary heart disease (CHD) is not known. We have developed a sandwich ELISA that enables apo J to be assayed in the range of 13-200 microg/mL. Serum apo J was 52.8+/-0.8 microg/mL (mean+/-SEM; range, 36.0-84.3 microg/mL; n=92) in healthy Japanese men, and 49.3+/-0.5 microg/mL (34.5-72.8; n=241) in healthy Japanese women. Multiple regression of these data and results from 67 men with CHD showed that apo J concentration was unrelated to age, sex or body mass index, but was positively related to serum PON1 (p<0.001) and apo B (p<0.02) concentrations. In women, it was also positively related to blood glucose (p<0.02). After adjusting for its associations with covariates, serum apo J averaged 5.4 microg/mL, lower in CHD men than in controls (p<0.003). Type 2 diabetics had higher apo J concentrations (men, 83.1+/-3.4 microg/mL, n=64; women, 64.0+/-2.3 microg/mL, n=46) than healthy men and women (p<0.001). In these Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but was positively related to blood glucose (p<0.01). After adjustment for its relation to blood glucose, the mean apo J concentration was similar in diabetics and healthy subjects. These findings suggest that apo J may be anti-atherogenic in humans, and that its concentration is raised by Type 2 diabetes.

Infection with Chlamydia pneumoniae but not Helicobacter pylori is related to elevated apolipoprotein B levels

Objective — Results of many studies show that apolipoprotein B (apo B) is a better marker of risk of vascular disease than other lipid markers including LDL and HDL-cholesterol and triglycerides. We investigated the association between two infectious agents: C. pneumoniae and H. pylori, known to have an atherogenic effect, and apo B, to evaluate the effects of chronic infections on apo B levels.Methods and results — The study group consisted of 257 patients in whom diagnostic coronary angiography was performed. C. pneumoniae IgG and IgM and H. pylori IgG and IgA antibodies were measured by enzyme-linked immunosorbent assay and apo B levels were measured by the nephelometry method. Established risk factors of atherosclerosis were recorded.Of 257 patients recruited, 104 had normal vessels, 88 had 3 or more vessels obstructed and 65 had ectatic vessels without atherosclerosis. Mean apo B concentration was significantly higher in C. pneumoniae IgG and IgM positive healthy subjects compared with C. pneumoniae negatives (0.954 vs. 0.722 and 0.973 vs. 0.851, p < 0.001 and p = 0.007, respectively). Apo B levels were significantly higher in severe atherosclerotic patients (0.985 ± 0.234 g/l) compared with control subjects (0.892 ± 0.244 g/l) (p = 0.008), but the difference was not significant in ectatic subjects (0.946 ± 0.272 g/l) when compared with controls (p = 0.18). Apo B levels were higher but not statistically significant in H. pylori antibody positive cases when compared with negatives.Conclusions — Apo B levels increased with C. pneumoniae infection. This finding supports the hypothesis that lipid profiles change to atherogenic lipid profile in chronic infections.

First measurements of the latitudinal atmospheric O2 and CO2 distributions across the western Pacific

We examine the latitudinal distribution of the tracer “atmospheric potential oxygen” APO = O2 + 1.1 × CO2 between 40°S and 50°N using new atmospheric CO2 and O2 measurements from flask samples collected onboard cargo ships between Japan and the United States, and Japan and Australia (or New Zealand) during the period from December 2001 to August 2004. Because APO is unaltered during photosynthesis and respiration by land vegetation, its atmospheric distribution is tightly linked to the air‐sea gas exchange of O2 and CO2 and the underlying processes. We find that the seasonal amplitude of APO increases towards high latitudes in both hemispheres and its minimum is located approximately 10‐degree north of the equator. The latitudinal distribution of annual mean APO shows a maximum in the tropics, confirming the recent coupled ocean‐atmosphere model predictions for this region.

Lipid parameters in childhood cirrhosis and chronic liver disease

Alterations in lipid metabolism are well defined in liver disease. As there has not been an ample amount of work published regarding this topic in children, especially about apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B), theoretical knowledge depends on adult studies. In this study, we investigated serum lipid parameters of children with chronic liver disease and cirrhosis. Serum triglyceride, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), plasma apo A-I and apo B levels of 82 children with chronic liver disease, 41 of whom had cirrhosis as well, were investigated. Twenty healthy children were selected as controls. While mean serum triglyceride and cholesterol levels were not different in chronic hepatitis, cirrhosis and healthy children, mean apo B level of cirrhotic group was higher than that of the control group (P < 0.05). Mean LDL and HDL values of children with chronic hepatitis were lower and mean apo B value was higher than those of the control group (P < 0.05, P < 0.05 and P < 0.001, respectively). Apolipoprotein A-I level was lower in cholestatic cirrhotic children than non-cholestatic children (P < 0.05). No statistical difference was detected in lipid parameters of children with or without malnutrition (P > 0.05). The mean HDL value of Child-Pugh B group was significantly lower when compared to Child-Pugh A group (P < 0.05). The mean apo A-I value of Child-Pugh A group was higher than those of Child-Pugh B and C groups (P < 0.05 and P < 0.001). Consequently, we found that among lipid parameters apo A-I was the most affected parameter in liver injury. Whether apo A-I level can be used as a prognostic criterion in childhood cirrhosis may require further study.

Apolipoprotein E in Apolipoprotein B (apo B)- and Non-apo B-containing Lipoproteins in 3523 Participants in the Stanislas Cohort: Biological Variation and Genotype-specific Reference Limits

Apolipoprotein (apo) E is a component of two major classes of plasma lipoproteins, apo B- (apo E-LpB) and non-apo B-containing (apo E-Lp-non-B) lipoproteins. The factors that affect total apo E in particles [lipoprotein E (LpE), apo E-Lp-non-B, and apo E-LpB], are incompletely characterized. We studied the determinants of these lipoparticles in a sample population of presumably healthy individuals: 1784 children (age range, 8-18 years) and 1739 adults (age range, 19-50 years). Serum concentrations of LpE and apo E-Lp-non-B were measured by electroimmunoassays, and the concentration of apo E-LpB was calculated by a difference method. Serum LpE and apo E-Lp-non-B were higher in females than in males. Their concentrations decreased with age until 20-25 years and then increased in men but not in women. apo E-LpB concentrations increased up to 20-25 years and were similar in both sexes. Thereafter, adult men had higher values than women. Individuals carrying the epsilon2 allele had higher mean apo E-Lp-non-B concentrations and lower apo E-LpB concentrations than did individuals carrying the epsilon3 allele. Individuals with the epsilon4 allele showed an inverse profile compared with those with the epsilon2 allele. Age, gender, the common apo E polymorphism, puberty, serum lipid concentrations, and alcohol consumption were significantly associated with total LpE, apo E-Lp-non-B, and apo E-LpB concentrations. Reference limits were established according to age, gender, and the common apo E polymorphism. Because measurements of LpE, apo E-Lp-non-B, and apo E-LpB concentrations may improve cardiovascular risk assessment, the proposed reference limits will aid interpretation of the results in clinical or therapeutic trials.

Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and plasma

Apolipoprotein (apo) A-IV is a major component of triacylglycerol-rich lipoprotein (TRL) apolipoproteins. We investigated the effects of dietary saturated fat and cholesterol restriction on the metabolism of TRL and plasma apo A-IV. We assessed TRL and plasma apo A-IV kinetics in 16 and 4 subjects, respectively, consuming an average US (baseline) diet for 6 wk and a National Cholesterol Education Program Step II diet for 24 wk, respectively. At the end of each diet period, all subjects received a primed, constant infusion of deuterated leucine for 15 h with hourly feeding. Ratios of stable-isotope tracer to tracee were measured by using gas chromatography-mass spectrometry, and kinetic data were modeled by using SAAM II. Mean apo A-IV concentrations during the isotope infusion period were 6.9 +/- 2.6 mg/L in TRL and 2.2 +/- 3.2 mg/L in plasma with the baseline diet; these values were 37.7% (P < 0.001) and 19.4% (P < 0.01) lower with the Step II diet. Similar changes were observed in the fasting state between the 2 diets. The mean apo A-IV secretion rate decreased significantly from baseline by 59.6% in TRLs and by 40.2% in plasma. Significant correlations were observed between TRL apo A-IV concentrations and the secretion rate (r = 0.94, P < 0.001) and between TRL apo A-IV pool size and TRL-cholesterol concentrations (r = 0.48, P < 0.01). Our data indicate that the National Cholesterol Education Program Step II diet significantly decreases TRL and plasma apo A-IV concentrations compared with the average US diet and that this decrease is due to a decreased secretion rate.

Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygous subjects for apo A-I Zaragoza (L144R)

We have recently reported a new apolipoprotein (apo) A-I variant (apo A-I(Zaragoza) L144R) in a Spanish family with HDL-C levels below the 5th percentile for age and sex and low apo A-I concentrations. All the apo A-I(Zaragoza) subjects were heterozygous and none of them showed evidence of coronary artery disease (CAD). Mean plasma HDL-C, apo A-I, and apo A-II levels were lower in apo A-I(Zaragoza) carriers as compared to control subjects (40, 60, and 50%, respectively). Lipid composition analysis revealed that apo A-I(Zaragoza) carriers had HDL particles with a higher percentage of HDL triglyceride and a lower percentage of HDL esterified cholesterol as compared to those of control subjects. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate of apo A-I(Zaragoza) carriers were normal. Apo A-I and apo A-II metabolic studies were performed on two heterozygous apo A-I(Zaragoza) carriers and on six control subjects. We used a primed constant infusion of [5,5,5-2H3]leucine and HDL apo A-I and apo A-II tracer/tracee ratios were determined by gas chromatography mass spectrometry and fitted to a monoexponential equation using SAAM II software. Both subjects carrying apo A-I(Zaragoza) variant showed mean apo A-I fractional catabolic rate (FCR) values more than two-fold higher than mean FCR values of their controls (0.470+/-0.0792 vs. 0.207+/-0.0635 x day(-1), respectively). Apo A-I secretion rate (SR) of apo A-I(Zaragoza) subjects was slightly increased compared with controls (17.32+/-0.226 vs. 12.76+/-3.918 mg x kg(-l) x day(-1), respectively). Apo A-II FCR was also markedly elevated in both subjects with apo A-I(Zaragoza) when compared with controls (0.366+/-0.1450 vs. 0.171+/-0.0333 x day(-1), respectively) and apo A-II SR was normal (2.31+/-0.517 vs. 2.1+/-0.684 mg x kg(-l) x day(-1), respectively). Our results show that the apo A-I(Zaragoza) variant results in heterozygosis in abnormal HDL particle composition and in enhanced catabolism of apo A-I and apo A-II without affecting significantly the secretion rates of these apolipoproteins and the LCAT activation.

Lipoprotein abnormalities in patients with secondary renal amyloidosis.

The prevalance of hyperlipidemia in chronic renal failure (CRF) patients is higher than in general population. Secondary amyloidosis is a common cause of CRF in Turkey. In this study, 25 patients with CRF due to secondary renal amyloidosis (amyloid-CRF), 15 patients with CRF without amyloidosis-CRF and 17 healthy controls were studied for serum lipid parameters. The mean serum lipoprotein (a) [LP(a)] level in the patients with amyloid-CRF was significantly higher than in the controls (p < 0.01). The mean serum apolipoprotein B (Apo B), apolipoprotein E (Apo E) and triglyceride levels in the patients with amyloid-CRF were very significantly higher than in the controls (p < 0.001). The mean serum total cholesterol, low-density lipoprotein (LDL) levels in the patients with amyloid-CRF were higher than in the controls (p < 0.05). The mean serum apo AI levels in the patients with amyloid-CRF was very significantly lower than in the controls (p < 0.001). The mean serum high-density lipoprotein (HDL) in the patients with amyloid-CRF was lower than in the controls (p < 0.05). The mean serum Lp (a), Apo AI, Apo B and Apo E levels in the patients with amyloid-CRF were significantly higher than in the patients with CRF (p < 0.01). The mean serum total cholesterol, trigliserides, LDL and HDL levels in the patients with amyloid-CRF were higher than in the patients with CRF (p < 0.05). There was not any correlation with serum lipid parameters and serum albumin and urine protein levels (p > 0.05). Our study suggests that serum lipid parameters are abnormal and might be the risk factor of atherosclerotic vascular disease and contribute to renal disease progression in the patients with secondary renal amyloidosis and lipid abnormalities were different from CRF with various etiology, without amyloidosis.

Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial

In this nested case-control study, lipoprotein (a) [Lp(a)] concentrations and apo(a) isoform size were measured in serum samples obtained from men participating in the prospective Multiple Risk Factor Intervention Trial (MRFIT). Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a) levels ( n=736) and isoform size ( n=487), respectively. Cases involved nonfatal myocardial infarctions (MI; n=98), documented during the active phase of the study that ended on February 28, 1982 and coronary heart disease (CHD) deaths ( n=148) monitored through 1990. Median Lp(a) levels did not differ between cases and controls and mean apo(a) size did not vary between cases and controls in the entire study population. When adjusted for age and Lp(a) concentration, logistic regression analysis indicated that small apo(a) isoforms were associated with CHD deaths among smokers (OR 3.31; 95% CI 1.07–10.28).

Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM Study

Lp(a) concentrations are largely determined by apo(a) isoform size, but several studies have shown that apo(a) isoforms could not entirely explain the increase of Lp(a) levels observed in patients with coronary heart disease (CHD). Since up to 90% of the variance in Lp(a) levels has been suggested to be attributable to the apo(a) locus, the hypothesis that polymorphisms of the apo(a) gene other than size could contribute to the increase of Lp(a) levels in CHD patients must be considered. This hypothesis was tested in the ECTIM Study comparing 594 patients with myocardial infarction and 682 control subjects in Northern Ireland and France. In addition to apo(a) phenotyping, five previously described polymorphisms of the apo(a) gene were genotyped: a (TTTTA) n repeat at position −1400 from the ATG, a G/A at −914, a C/T at −49, a G/A at −21 and a Met/Thr affecting amino acid 4168. As reported earlier [Parra HJ, Evans AE, Cambou JP, Amouyel P, Bingham A, McMaster D, Schaffer P, Douste-Blazy P, Luc G, Richard JL, Ducimetiere P, Fruchart JC, Cambien F. A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM study. Arterioscler Thromb 1992;12:701–707], mean Lp(a) levels were higher in cases than in controls (20.7 vs 14.6 mg/dl in Belfast, 17.2 vs 8.9 mg/dl in France, P<0.001 for case-control and population differences). In the present study, mean apo(a) isoform size differed significantly between cases and controls (25.7 vs 26.6 kr in Belfast, 25.9 vs 27.4 kr in France, P<0.001 for case-control and P=0.13 for population difference). After adjustment for apo(a) isoforms, Lp(a) levels remained significantly higher in cases than in controls (difference, 4.6 mg/dl; P<0.001). Genotype and allele frequencies did not differ significantly between cases and controls for any of the five polymorphisms studied. The five polymorphisms were in strong linkage disequilibrium and had a combined heterozygosity of 0.83. In multivariate regression analysis adjusted for apo(a) isoforms, only the (TTTTA) n polymorphism was significantly associated with Lp(a) levels; it explained 4.5% of Lp(a) variability in cases and 3.1% in controls. The Lp(a) case/control difference was not reduced after taking into account the (TTTTA) n effect. We conclude that the increase of Lp(a) levels observed in MI cases, and which was not directly attributable to apo(a) size variation, was not related to the five polymorphisms of the apo(a) gene considered.