RESUMO
We describe here seven cases (from five kindreds) of Anderson's disease, which is characterized by diarrhea, steatorrhea, hypobetalipoproteinemia with low levels of cholesterol, triglycerides, and phospholipids, and failure to secrete chylomicrons after a fat meal. Enterocytes isolated from intestinal biopsies of patients after overnight fast showed numerous fat droplets, a histological picture resembling that of abetalipoproteinemia. Immunoenzymatic staining of the enterocytes demonstrated large amounts of material that reacted with a polyclonal antiserum to apolipoprotein B. Further, the immunoreactive material was found to react with several different monoclonal antibodies capable of recognizing both the B100 and B48 forms of apoprotein B, but not with any of several monoclonal antibodies capable of recognizing only B100. This suggests that the material in the enterocytes is the B48 form of apoprotein B or a fragment thereof. Additional findings included decreased low density lipoprotein levels with an abnormal chemical composition, abnormal high density lipoprotein2 (HDL2) and HDL3 particle size distributions, and an abnormal HDL apoprotein composition. Increased amounts of proteins having electrophoretic mobilities similar to apo E and the E-AII complex were present. Finally, some cases exhibited additional protein components of apparent molecular weights between 17,000 and 28,000, which was similar to some cases of abetalipoproteinemia. These findings demonstrate that Anderson's disease is not due to the absence of synthesis of intestinal apo B and suggest that it is more complex than previously thought, affecting all the lipoprotein classes.
Assuntos
Abetalipoproteinemia/metabolismo , Apolipoproteínas B/metabolismo , Mucosa Intestinal/metabolismo , Abetalipoproteinemia/patologia , Adolescente , Apolipoproteínas B/análise , Compostos Azo , Transporte Biológico , Criança , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Técnicas Imunoenzimáticas , Mucosa Intestinal/análise , Mucosa Intestinal/ultraestrutura , Lipídeos/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Coloração e RotulagemRESUMO
Anderson's disease is a recessive disorder characterized by intestinal fat malabsorption, absence of postprandial chylomicrons, and reduced levels of cholesterol, triglycerides, and apoproteins B, AI, and C. We have studied two families with, respectively, three and two children with Anderson's disease. Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in size but their concentration was decreased fivefold compared with controls. After DNA digestion with seven restriction enzymes, restriction fragment length polymorphisms of apo-B gene did not show conclusive information except for Xba1, which revealed a lack of cosegregation between the restriction fragment length polymorphism and the Anderson's phenotype. Linkage analysis was performed using the polymorphism of the apo-B gene 3'minisatellite. Genomic DNA from parents and children was amplified by polymerase chain reaction using oligonucleotide primers flanking the apo-B gene 3'hypervariable locus. In both families each child inherited different apo-B alleles from at least one parent. According to the recessive mode of transmission of the disease, our results are incompatible with the involvement of the apo-B gene. More likely a posttranslational defect or a mutation in another gene encoding a protein essential for lipoprotein assembly or secretion may be involved.
Assuntos
Apolipoproteínas B/genética , Quilomícrons/metabolismo , Síndromes de Malabsorção/genética , Adolescente , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and viral hepatitis are associated with hepatic oxidative stress, which is partially dependent on the amount of hepatic fat. AIM: To determine whether the circulating lipid and oxidative stress parameters could be non-invasive markers of hepatic steatosis. METHODS: Sixty-four patients with NAFLD or viral hepatitis were tested for lipid peroxidation products and antioxidant defence systems, lipid parameters and liver function tests. RESULTS: Hepatic steatosis was correlated with lipids, gamma-glutamyltranspeptidase, thiobarbituric acid-reactive substances, superoxide dismutase and superoxide dismutase/erythrocyte glutathione peroxidase ratio. gamma-Glutamyltranspeptidase, triglycerides and low-density lipoprotein cholesterol were significantly higher in the presence of steatosis. No difference in blood oxidative stress markers was observed according to the presence or absence of steatosis except for the superoxide dismutase/erythrocyte glutathione peroxidase ratio. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were significantly higher in the NAFLD group (n = 17, 60% mean steatosis grade) than in the viral hepatitis group (n = 20, 13% mean steatosis grade). Only superoxide dismutase was lower and vitamin E higher in NAFLD than in viral hepatitis patients. CONCLUSIONS: Standard blood oxidative stress markers do not predict the extent of hepatic steatosis as they probably do not accurately reflect intrahepatic oxidative stress. Serum lipid levels were best correlated with hepatic steatosis.
Assuntos
Biomarcadores/análise , Fígado Gorduroso/metabolismo , Hepatite C Crônica/metabolismo , Estresse Oxidativo , Adulto , Colesterol/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Selênio/sangue , Superóxido Dismutase/sangue , Vitamina E/sangueRESUMO
We describe an ELISA technique able to recognize malondialdehyde-modified low-density lipoproteins (LDL). For this purpose we produced antibodies to malondialdehyde-LDL, specific for the malondialdehyde modification of LDL; these antibodies recognized essentially malondialdehyde-LDL. Coating ELISA plates with the antibodies to malondialdehyde-LDL and using peroxidase-labelled antibodies to LDL, which reveal only apolipoprotein B, we obtained an accurate method of detecting malondialdehyde-modified apolipoprotein B. Preliminary studies demonstrated that this method allows the detection of lipoproteins containing malondialdehyde-modified apolipoprotein B in the serum of patients with cardiovascular diseases.
Assuntos
Lipoproteínas LDL/imunologia , Malonatos , Malondialdeído , Animais , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Imunodifusão , Lipoproteínas LDL/análise , Monócitos/imunologia , CoelhosRESUMO
International guidelines emphasize the importance of LDL cholesterol (LDL-C) assay in the care and follow-up of patients with cardiovascular risk. Most studies and common practice use Friedewald's formula for LDL-C calculation. The accuracy of the result depends closely on the precision of the input parameters (total cholesterol, triglycerides (TG) and HDL cholesterol), and discrepancies between calculated LDL-C and measurement by reference methods appear when TG exceed 4.5 mmol/L, or in the presence of abnormal lipoproteins. These restrictions and uncertainties in calculations have prompted the recent development of direct and homogeneous methods that fit all analyzers. A multicenter evaluation of four direct assays of LDL-C (Daiichi, Denka Seiken, Kyowa, Wako) was carried out on 45 serum samples (TG below 3.1 mmol/L) in eight laboratories using different analyzers. For three methods (Daiichi, Kyowa, Wako), the interlaboratory reproducibility was markedly improved relative to that of calculation. A strong correlation was found for all new methods when compared with a beta-quantification assay. Average bias in Denka Seiken assays was greater than Kyowa's and Daiichi's (although less dispersed for the latter) and for Wako all bias were positive. The relationship between bias variations and the lipid parameters of the samples was studied. Three methods, Daiichi, Kyowa and Wako, revealed a significant positive correlation between bias and serum VLDL-C/TG ratio, clearly indicating that cholesterol enrichment of VLDL was a source of variability in these assays. Specificity of the four methods was tested in situation of dyslipidemia by spiking isolated lipoproteins (chylomicrons, VLDL and HDL). This experiment revealed differences in behavior, most evidently upon addition of VLDL. No method was truly specific, but up to 8 mmol/L of TG the variations were acceptable. In the presence of type III hyperlipoproteinemia, however, only the Denka Seiken method was reliable. Linearity up to 20 mmol/L (Daiichi, Denka Seiken) or 14 mmol/L (Kyowa, Wako) of LDL-C allows these tests to be used in main routine cases. New direct assays are an obvious technological advance in terms of analytical performance and conveniency. Their use for the diagnosis and follow-up of hyperlipidemic patients offers an alternative that overcomes the limitations of the Friedewald calculation.
Assuntos
LDL-Colesterol/sangue , Análise Química do Sangue/métodos , Colesterol/sangue , Humanos , Hiperlipoproteinemias/sangue , Laboratórios , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Triglicerídeos/sangueRESUMO
Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).
Assuntos
Esclerose Lateral Amiotrófica/genética , Apolipoproteínas E/genética , Adulto , Idoso , Esclerose Lateral Amiotrófica/sangue , Apolipoproteínas E/sangue , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Intervalos de Confiança , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
Plasma-lipoproteins isolated between d 1.020 and d 1.055 g/ml were partially delipidated with ethyl ether at 4 degrees C. This treatment induces a transformation of the lipoproteins which is evolutive during several days. Bidimensional immunoelectrophoresis reveals the lipoproteins dissociation and the appearance of 4 immunologically different fractions. The time dependent formation of these subunits is slowed down by EDTA and less efficiently by antioxydants. Once started, the dissociation can be accelerated by heating at 37 degrees C or by UV exposition. Another lipopeptide is more easily revealed by anti VLDL antiserum. It can be shown in the native and in the partially or completely delipidated LDL. Its presence does not depend on lipoprotein dissociation.
Assuntos
Lipoproteínas LDL/sangue , Humanos , Imunodifusão , Imunoeletroforese Bidimensional , Lipoproteínas LDL/análise , Peptídeos/análiseRESUMO
Low density lipoproteins (d = 1.030-1.055) were partially delipidated with ethyl-ether (LDLe). These LDLe exhibit a spontaneous dissociation several days after delipidation. Four different immunoprecipitation complexes (B-I to B-IV) are observed when using two dimensional immunoelectrophoresis against anti LDLe immunserum. The various subunits of LDLe have different behaviour upon electrophoresis. On disc gel electrophoresis containing urea three bands can be seen; all are phospholipoproteins. The apolipoprotein moiety of LDL and LDLe have the same apparent molecular weight around 550 000. With time several subunits appear in LDLe, the majority of them have a molecular weight around 370 000, 260 000 and 125 000. One of the components from dissociated LDLe containing the immunodeterminant B-III, has been separated by chromatography on heparin-agarose. This LDLe-B-III has the same phospholipid/protein ratio as total LDLe and a protein moiety with an apparent molecular weight of 110 000. This part of apolipoprotein B has no affinity for heparin. Immunocompetition studies by the ELISA technique indicated that sialic acid, one of terminal residues of LDL glycoprotein, is involved in the immunological recognition of LDL and of its derivatives by anti LDL and anti LDLe antisera.
Assuntos
Lipoproteínas LDL/sangue , Aminoácidos/análise , Complexo Antígeno-Anticorpo , Eletroforese em Gel de Poliacrilamida , Epitopos/análise , Hexoses/análise , Humanos , Soros Imunes , Imunoeletroforese , Substâncias Macromoleculares , Peso Molecular , Fosfolipídeos/análise , Ácidos Siálicos/análiseRESUMO
Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle.
Assuntos
Apolipoproteínas B/genética , Quilomícrons/sangue , Edição de RNA , RNA Mensageiro/genética , Apolipoproteína B-48 , DNA Complementar/biossíntese , Feminino , Humanos , Masculino , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Rare nonsynonymous mutations in the apolipoprotein A-I (apo A-I) gene are associated with low HDL-cholesterol levels. Despite the inverse correlation of high density lipoprotein (HDL)-cholesterol levels with the risk of coronary heart disease (CHD) in the population, reduced circulating concentrations of HDL do not necessarily predispose to premature CHD. One apo A-I defect was even reported to cause longevity. We describe a French patient who presented with very low serum HDL-cholesterol levels (10 mg/dl). Sequence analysis of the apo A-I gene identified a heterozygous mutation in the apo A-I gene which causes a cysteine for arginine replacement at residue 151. Family members with the mutation displayed 50% lower levels of plasma HDL-cholesterol and of apo A-I than unaffected members. Plasma activity of lecithin:cholesterol acyl transferase (LCAT) was significantly lower in apo A-I(R151C) heterozygotes than in controls. Furthermore, we found that as for apo A-IMilano (R173C), apo A-I(R151C) forms heterodimers with apo A-II. Moreover, HDL particles were abnormal in both lipid composition and size distribution. Despite these quantitative and qualitative differences in HDL, neither the history of the family over three generations nor the examination of the patient, gave any indication of premature occurrence of atherosclerosis or CHD. We conclude that apo A-I(R151C) causes a phenocopy of apo A-IMilano (R173C), an apo A-I variant which is assumed to cause longevity and which is considered as a potentially anti-atherogenic agent.
Assuntos
Apolipoproteína A-I/genética , Mutação Puntual , Adulto , Idoso , Apolipoproteína A-I/sangue , Arginina/genética , Criança , HDL-Colesterol/sangue , HDL-Colesterol/genética , Doença das Coronárias/sangue , Doença das Coronárias/genética , Cisteína/genética , Eletroforese , Feminino , Heterozigoto , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Fatores de Risco , Análise de Sequência de DNA , Doença de Tangier/sangue , Doença de Tangier/genéticaRESUMO
A new rare apolipoprotein E mutant was identified as we were investigating the apolipoprotein E genotype of patients with type III hyperlipidemia (HLP III). The unusual DNA restriction fragment length polymorphism profile and then the sequence analysis of a PCR amplified fragment of the proband's apo E gene revealed a simple base substitution (G-->T) at nucleotide 3836. This mutation leads to the replacement of arginine by leucine at position 142 of the mature protein. The proband carried the mutant allele at the heterozygous status with an epsilon 3 allele. Subsequently, analysis of the proband's father's apo E gene showed that same mutated allele associated with an epsilon 2 allele. The two subjects presented a dysbetalipoproteinemia in which this new apo E variant could be implicated.
Assuntos
Sequência de Aminoácidos , Apolipoproteínas E/genética , Hiperlipoproteinemia Tipo III/genética , Análise de Sequência de DNA , Idoso , Ácido Clofíbrico/análogos & derivados , Ácido Clofíbrico/uso terapêutico , Ácidos Fíbricos , Genótipo , Humanos , Hiperlipoproteinemia Tipo III/sangue , Hiperlipoproteinemia Tipo III/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fenótipo , Polimorfismo de Fragmento de RestriçãoRESUMO
The aims of the present study were (i) to characterize the HDL2, HDL3 and the LpA-I, LpA-I:A-II distribution, (ii) to investigate the prevalence of atherosclerotic lesions and (iii) to assess the activity of cholesteryl ester transfer protein (CETP) in 29 hyperalphalipoproteinemic (HALP) patients (HDL-C=90+/-11 mg/dl) with combined hypercholesterolemia (LDL-C=180+/-16 mg/dl). According to the HDL2/HDL3 and LpA-I/LpA-I:A-II ratios, two HALP profiles (A and B) were defined: in 22 patients (HALP profile A) these ratios were increased compared to the normolipidemic control subjects (1.19+/-0.11 versus 0.53+/-0.19, P < 0.001 and 1.01+/-0.2 versus 0.51+/-0.25, P < 0.001, respectively) and in seven patients (HALP profile B) these ratios were within the normal range (0.64+/-0.20 and 0.69+/-0.2, respectively). The atherosclerotic lesions were assessed by ultrasonography of the carotid arteries. Amongst patients with HALP profile A, 17 were free from lesions, five had intimal wall thickening and none displayed plaques, whereas for patients within the HALP profile B, only one was free from lesions, two had intimal wall thickening and four displayed plaques. CETP activities (348+/-116 versus 371+/-75%/ml/h) and CETP concentrations (2.4+/-0.5 versus 2.5+/-0.6 microg/ml) were similar in HALP profiles A and B, however these values were both higher than in control subjects (190+/-40%/ml/h, P < 0.001 and 1.8+/-0.3 microg/ml, P < 0.001, respectively). Hence the hyperalphalipoproteinemic profiles (A and B) described here were not related to CETP deficiency. In conclusion, the HALP profile A was characterized by both increased HDL2/HDL3 and LpA-I/LpA-I:A-II ratios and was associated with a low prevalence of atherosclerosis, whereas the HALP profile B, characterized by HDL2/HDL3 and LpA-I/LpA-I:A-II ratios within the normal range, was less cardioprotective.
Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas , Hiperlipoproteinemias/sangue , Lipoproteínas HDL/sangue , Adulto , Apolipoproteína A-I/análise , Apolipoproteína A-II/análise , Proteínas de Transferência de Ésteres de Colesterol , Feminino , Humanos , Hiperlipoproteinemias/fisiopatologia , Lipoproteínas HDL/química , Masculino , Pessoa de Meia-IdadeRESUMO
High serum levels of cholesterol and triglycerides are risk factors for coronary heart disease and are strongly related to several haemostatic parameters. Thyroid disorders are a frequent feature in hyperlipidemic patients and are also associated with a variety of haemostatic abnormalities. Therefore, we analysed the relationships between free T4 (fT4) levels and Factor VII and VIII activities (FVIIc and FVIIc), D-Dimers (DDI) and Plasminogen Activator Inhibitor type 1 (PAI-1), in a group of 472 healthy patients referred for hyperlipidemia. Fourty patients were found to have primary hypothyroidism. A negative correlation was found in the whole study population between fT4 and DDI (p = 0.0001, r = -0.21) and the same results were found after exclusion of the patients with fT4 below the normal range (p = 0.0007, r = -0.17). In a multivariate regression analysis, the relationship between DDI and fT4 was independent of age, Body Mass Index (BMI), gender and total cholesterol. Less impressive correlation coefficients were found with FVIIc (r = -0.10), FVIIIc (r = -0.09) and PAI-1 (r = -0.09). These results suggest that fT4 may play a physiological role in the regulation of the haemostatic equilibrium in hyperlipidemic patients and that low levels of fT4 are associated with a hypercoagulable state.
Assuntos
Coagulação Sanguínea/fisiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinólise/fisiologia , Hiperlipidemias/sangue , Tiroxina/sangue , Adolescente , Adulto , Idoso , Arteriosclerose/sangue , Biomarcadores/sangue , Fatores de Confusão Epidemiológicos , Fator VII/metabolismo , Fator VIII/metabolismo , Feminino , Hemostasia/fisiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/metabolismoRESUMO
A positive exercise electrocardiogram (ECG) is not infrequent occurrence in asymptomatic hypercholesterolemic patients, but the number of false-positive tests may be relatively high (50%). Therefore, the ability of a positive stress ECG to predict coronary artery lesions is low even in populations with > or =1 cardiovascular risk factors. To increase the diagnostic value of exercise tests for screening asymptomatic individuals, we analyzed whether combined clinical parameters with carotid echography would accurately predict coronary atherosclerotic lesions by coronary angiography in asymptomatic hypercholesterolemic patients with a positive exercise ECG. Seventy-six asymptomatic patients (between 35 and 65 years of age) with hypercholesterolemia (total plasma cholesterol >6.5 mmol/L or 250 mg/dl) and a positive stress ECG were referred for carotid B-mode echography and coronary angiography. Carotid echography data were divided into 2 categories: (1) absence of any atherosclerotic plaque, or (2) presence of > or =1 arterial plaques. Coronary stenosis assessed by coronary angiography was considered to correspond to a > or =50% reduction of coronary lumen diameter. Forty-three patients (57%) displayed coronary lesions; most (38; 88%) had carotid plaque. Multivariate analysis showed that the presence of carotid plaque was significantly associated with coronary stenosis (odds ratio 15.2; confidence interval 5.0 to 54.5). In subgroups characterized by high frequency of false-positive exercise electrocardiographic tests (women and patients with a 10-year predicted risk of coronary artery disease [CAD] <15%), none of the patients without carotid plaque exhibited coronary lesions. Echographic evaluation of carotid plaque (plaque vs no plaque) significantly improved the diagnostic specificity of exercise electrocardiography. We conclude that the combination of clinical, electrical, and echographic data facilitates cost-effective noninvasive detection of CAD in asymptomatic hypercholesterolemic patients.
Assuntos
Estenose das Carótidas/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Hipercolesterolemia/complicações , Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/complicações , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Eletrocardiografia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , UltrassonografiaRESUMO
The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.
Assuntos
Doença da Artéria Coronariana/metabolismo , Glicoproteínas , Lipase/metabolismo , Lipoproteínas HDL/sangue , Fígado/enzimologia , Proteínas de Transferência de Fosfolipídeos , Adulto , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/metabolismo , Proteínas de Transporte/sangue , Proteínas de Transferência de Ésteres de Colesterol , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/enzimologia , Feminino , Humanos , Lipídeos/sangue , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Razão de Chances , Prevalência , UltrassonografiaRESUMO
We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.
Assuntos
Apolipoproteínas B/sangue , Apolipoproteínas C/sangue , Glicoproteínas , Hiperlipoproteinemias/sangue , Lipoproteínas HDL/sangue , Período Pós-Prandial/fisiologia , Adulto , Apolipoproteína C-III , Apolipoproteínas E/sangue , Proteínas de Transporte/análise , Proteínas de Transferência de Ésteres de Colesterol , Feminino , Humanos , Lipase Lipoproteica/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
The lipid composition and apopeptide patterns of plasma LDL and VLDL have been studied in a patient with LCAT deficiency, using two-dimensional immunoelectrophoresis. After absorption of a fat meal an elevation of VLDL apopeptides C was observed. Apo-LDL also showed an abnormal relative increase of apo-C. After heparin-induced lipolysis, a shift of apo-C from chylomicra and VLDL to LDL was noticed by the striking increase of apo-C in this last lipoprotein class. In view of the present and previously published results the possible mechanisms involved in lipoprotein catabolism in LCAT deficiency are discussed.
Assuntos
Aciltransferases/deficiência , Deficiência da Lecitina Colesterol Aciltransferase , Erros Inatos do Metabolismo Lipídico/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Humanos , Imunoeletroforese , Lipoproteínas LDL/imunologia , Lipoproteínas VLDL/imunologiaRESUMO
Three monoclonal antibodies to human serum apolipoprotein (Apo) A-I (4A12, 4B11 and 2G11) were produced by Sanofi. They were directed to three distinct epitopes of the Apo A-I molecule, present on the surface of the lipoprotein particles. They were able to precipitate individually some lipoprotein units from the serum. Only the mixture of the three monoclonal antibodies could allow a precipitation of all Apo A-I containing particles. An electroimmunoassay using this oligoclonal mixture was assessed to standardize the Apo A-I measurement in serum. Results agreed well with those obtained by electroimmunoassays using polyclonal antisera. Moreover no pretreatment of serum samples with dissociating agents or detergents was required. Therefore, this specific, rapid (7-8 h), precise (within- and between-assay precisions were 4.25 and 3.1%, respectively) immunoassay is routinely available for apolipoprotein A-I measurement in serum.
Assuntos
Anticorpos Monoclonais , Apolipoproteínas A/sangue , Lipoproteínas/sangue , Afinidade de Anticorpos , Apolipoproteína A-I , Apolipoproteínas A/imunologia , Humanos , Imunoeletroforese , Lipídeos/sangueRESUMO
The measurement of the activity of cholesteryl ester transfer protein (CETP), is of high clinical interest and this study reports the use of a direct LDL isolation (d-LDL) technique to determine in one step the amount of radiolabeled cholesteryls esters ([3H]-CE) transferred from exogenous HDL3 to LDL, avoiding the conveniences of the usually used ultracentrifugation or precipitation of apo-B containing lipoproteins in the CETP methodologies. The d-LDL technique providing a specific immunoprecipitation of VLDL, IDL and HDL allowed to directly determine the [3H]-CE transferred on LDL (d-[3H]-CE-LDL). Two methodologies were assayed for the CETP activity using either exogenous or endogenous lipoproteins, and the results with the d-LDL technique were compared with those obtained using the ultracentrifugation (u-[3H]-CE-LDL) considered as the reference method. The intra- and inter-assays were similar in both techniques for the two CETP activity assays. Strong positive correlations were established between values obtained with d-[3H]-CE-LDL and u-[3H]-CE-LDL isolation procedures for CETP activities with exogenous or endogenous lipoproteins (r = 0.972; p = 0.0001 and r = 0.965; p = 0.0001 respectively). In conclusion, the d-LDL technique represents an easy and accurate procedure to measure directly, in normotriglyceridemic plasmas, the amount of [3H]-CE transferred from HDL to LDL by the CETP.
Assuntos
Proteínas de Transporte/sangue , Glicoproteínas , Lipoproteínas LDL/sangue , Lipoproteínas LDL/isolamento & purificação , Proteínas de Transferência de Ésteres de Colesterol , Ésteres do Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Hipercolesterolemia/sangue , Valores de Referência , Trítio , UltracentrifugaçãoRESUMO
Lipoproteins constitute in plasma a dynamic system allowing lipid transport. For this purpose, apolipoproteins play a very important part. They control and regulate lipid transfer between lipoproteins themselves and among cells, from their hepatic as intestinal synthesis sites to their hepatic as peripheral degradation sites. Enzymatic systems and specific receptors are involved to operate this metabolic pathway.