Lecitina colesterol aciltransferasa en mujeres postmenopáusicas y su relación con factores bioquímicos y antropométricos asociados a riesgo cardiovascular / Lecithin cholesterol acyltransferase in serum of postmenopausal women in relation to biochemical and anthropometric factors associated to cardiovascular risk

Resumen Objetivo: determinar los valores séricos de la enzima lecitina colesterol aciltransferasa en un grupo de mujeres postmenopáusicas, y establecer su relación con factores asociados a riesgo cardiovascular. Materiales y métodos: estudio descriptivo transversal prospectivo, correlacional, que incluyó 56 mujeres postmenopáusicas en quienes se evaluaron variables antropométricas y bioquímicas (perfil lipídico y glicemia basal) asociadas a riesgo cardiovascular y se correlacionaron con las concentraciones séricas de lecitina colesterol aciltransferasa. Resultados: los valores séricos promedio de dicha enzima fueron 7,89 ± 1,26 (g/ml. Las mujeres con valores de índice de masa corporal superior a 25 tienen niveles séricos de lecitina colesterol aciltransferasa significativamente mayores que aquellas que tienen índice de masa corporal normal. No se observaron relaciones significativas entre los niveles de lecitina colesterol aciltransferasa y las variables bioquímicas evaluadas. Conclusiones: este trabajo es uno de los primeros que evalúa los niveles séricos de lecitina colesterol aciltransferasa en mujeres postmenopáusicas del Caribe colombiano. Se encontró una relación significativa entre los niveles séricos de lecitina colesterol aciltransferasa y los valores de índice de masa corporal elevados. Se requieren nuevos estudios para entender mejor la relación entre los niveles séricos de lecitina colesterol aciltransferasa y el riesgo cardiovascular en mujeres postmenopáusicas.

Abstract Objective: To determine the serum levels of lecithin cholesterol acyltransferase in a group of postmenopausal women and to establish their relationship with factors associated with cardiovascular risk. Materials and methods: A descriptive, correlational and cross-sectional study was performed that included 56 postmenopausal women. Anthropometric and biochemical (lipid profile and baseline blood glucose) variables associated with cardiovascular risk were measured, and were correlated with the serum concentrations of lecithin cholesterol acyltransferase. Results: The mean serum level of lecithin cholesterol acyltransferase was 7.89 ± 1.26 (g/ml. The women with a body mass index greater than 25 had significantly higher serum levels of the enzyme than those that had a normal body mass index. No significant relationships were observed between the levels of lecithin cholesterol acyltransferase and the biochemical variables evaluated. Conclusions: This study is one of the first that has evaluated the serum levels of lecithin cholesterol acyltransferase in postmenopausal women of the Colombian Caribbean. A significant relationship was found between the serum levels of lecithin cholesterol acyltransferase and elevated values of the body mass index. Further studies are required for a better understanding of the relationship between the serum levels of lecithin cholesterol acyltransferase and cardiovascular risk in postmenopausal women.

Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes

We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios.

Avaliação de pacientes esquistossomóticos quanto ao conteúdo mineral ósseo, nível de magnésio corporal total e atividade da enzima lecitina: colesterol acetiltransferase em pós-esplenectomizados com auto-implante esplênico / Evaluation of bone mineral density, total magnesium level and activity of a lecithin enzyme, acetyl-cholesterol transferase of post-splenectomy schistosomal patients with splenic autograft

Nos portadores jovens de esquistossomose cirúrgica existe déficit do conteúdo mineral ósseo (BMD), ocasionando retardo no desenvolvimento estato-ponderal que melhora com os tratamentos clínico e cirúrgico. Contudo, alguns pacientes permanecem com déficit do BMD. Foi objetivo geral do presente trabalho estudar o papel do magnésio no metabolismo ósseo nos pacientes esquistossomóticos; foram avaliados os níveis séricos e urinários de magnésio, antes e após dose de saturação desse cátion, para verificação de possível déficit do mesmo nesses pacientes, além da possível associação dos níveis séricos e urinários de magnésio com os níveis da enzima lecitina colesterol acetiltransferase (LCAT). Foram incluídos 18 portadores de esquistossomose na forma hepatoesplênica, com idade variando entre 13 e 24 anos, média de 18,6 ± 2,9; 11 eram do sexo masculino e sete do feminino. Todos haviam-se submetido a tratamento cirúrgico, que consistiu de: esplenectomia, ligadura da veia gástrica esquerda e auto-implante de tecido esplênico, no epíploo maior. Esses pacientes foram tratados clínica e cirurgicamente no Serviço de Cirurgia Geral da Criança do Hospital das Clínicas da UFPE, no período de 1990 a 2001. Foi avaliado o BMD, antes e após tratamento clínico, com dose única de oxamniquine, e o tratamento cirúrgico. O BMD foi medido nas vértebras lombares (L2-L4), usando um densitômetro modelo LUNAR DPX-L®. Quatorze pacientes apresentaram BMD deficiente. O magnésio sérico e o urinário foram medidos antes e 24 horas após a infusão de dose de saturação desse íon (6mg/ kg de MgSO4). A deficiência de magnésio foi considerada quando a reabsorção desse íon era maior do que 40 por cento. Quatro pacientes (22,2 por cento) apresentaram depleção do magnésio. Não houve correlação entre os níveis de reabsorção de magnésio e os níveis de LCAT. Observou-se melhora no BMD no pós-operatório (p = 0,052), entretanto, sem alcançar significância estatística. Essa melhora esteve associada ao aumento, no pós-operatório, da LCAT. Embora o papel do magnésio no metabolismo ósseo, nos pacientes esquistossomóticos, não seja definitivo, os dados dão suporte ao conceito de que esse cátion deva ser considerado na correção do déficit de BMD desses pacientes.

Efeito de tratamento cirúrgico sobre a atividade da enzima hepática lecitina: colesterol aciltransperase (LCAT)na esquistossomose mansônica / Surgical treatment effect on the lecitin liver enzyme activity: cholesterol acyltransferase (LCAT) in schistosomiasis mansoni

A esquistossomose mansônica é uma doença tropical que constitui um importante problema de saúde pública, na Regiäo Nordeste do Brasil, onde é encontrada em alta endemicidade. Essa parasitose tem o fígado como principal alvo de suas lesöes histológicas, alteraçöes fisiopatológicas e manifestaçöes clínicas. Estudos anteriores reportam alteraçöes no metabolismo lipídico associadas à forma hepatoesplênica da esquistosomose.Uma das principais alteraçöes consiste na reduçäo da atividade da enzima hepática LCAT, responsável pela esterificaçäo do colesterol no plasma. Neste trabalho, avaliamos a atividade da LCAT no plasma de pacientes portadores da esquistossomose mansônica hepatoesplênica, os quais foram submetidos a esplenectomia e reimplante de parte de tecido do baço. A atividade enzimática da LCAT foi determinada com substrato radioativo. O [14C]colesterol livre e esterificado, formados por açäo da LCAT, foram separados por cromatografia em camada delgada e a radioatividade das amostras foi contada em analisador de cintilaçäo líquida. A atividade da LCAT nos pacientes submetidos a esplenectomia e reimplante de tecido do baço apresentou reduçäo de 32 por cento, em relaçäo ao grupo controle. Contudo, nos portadores da doença que näo foram submetidos ao procedimento cirúrgico a reduçäo na atividade da LCAT foi o dobro (64 por cento) da observada em pacientes esplenectomizados e com reimplante de parte do tecido do baço. Esses resultados sugerem haver uma melhora significativa no efeito da forma grave da esquistossomose mansônica sobre a atividade da LCAT.

Characterization and potential uses of rabbit polyclonal antibodies against human plasma lecithin-cholesterol acyltransferase

Familial and secondary deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) produce circulating lipoprotein particles with gross structural and compositional abnormalities; these have adverse effects on a variety of cellular functions. Factors affecting hepatic synthesis and secretion of this plasma enzyme are largely unknown but, potentially, some of them can be investigated with monospecific antibodies. In the present study, enzymically active LCAT was purified 40,000-fold from human plasma and then used to raise polyclonal antibodies in New Zealand White rabbits. Addition of this antiserum (1 mul) to human plasma (25 mul) completely inhibited LCAT activity, although it was less effective against plasma from other species. The antibodies appeared to be monospecific to plasma LCAT. They gave a single precipitin arc by crossed immunoelectrophoresis, while immunodiffusion established that there was no cross-reactivity with several apolipoproteins or with serum albumin. Moreover, the antiserum was successfully used to detect LCAT in normal human plasma by Laurell rocket immunoelectrophoresis. By contrast, Western blotting of plasma proteins using whole LCAT antiserum was largely unsuccessful because of high background staining, although this could be substantially reduced by use of an IgG fraction. However, the whole antiserum readily immunoprecipitated LCAT secreted into the culture medium of HepG2 cells, a human hepatoblastoma cell line, pre-labelled with [35S]methionine, the [(35)S]-labelled LCAT appearing as a narrow 65-kDa protein band by electrophoresis and fluorography. We conclude that polyclonal antibodies may be an important tool to investigate the characteristics and underlying mechanisms of secondary LCAT deficiencies, including those associated with hepatic cirrhosis and schistosomiasis.

Metabolismo de quilomicros / Chylomicron metabolism

O fígado exerce um importante papel no metabolismo dos quilomicros. É responsável pela síntese de apolipoproteínas (ex., apo AI, apo CII, apo E), lecitina-colesterol-acil-tranferase e lipase de remover os remanescentes de quilomicros da circulaçäo sangüínea. Näo é surpresa portanto que o metabolismo de quilomicros esteja comprometido nas doenças hepáticas tais como hepatite aguda, cirrose e colestase. Assim, sendo, os autores revisaram os aspectos normais do metabolismo dos quilomicros os quais säo essencias para uma melhor compreensäo das alteraçöes lipoprotéicas observadas nas doenças hepáticas

Relationship between lecithin: cholesterol acyltransfer and lipid and lipoprotein levels in plasma of mammals susceptible or resistant to atherosclerosis

The initial fractional and molar rates of lecithin:cholesterol acyltransfer and the plasma concentrations of unesterified and esterified cholesterol, total phospholipids, triacylglycerol, high density lipoprotein-cholesterol and aplipoprotein B-linked cholesterol were determined for young healthy women and for groups of female pigs, rabbits, rats and cattle. Coefficients were calculated for the simple and partial correlations between acyltransfer rates and lipid and lipoprotein concentrations. In all species molar acyltransfer rates were significantly corrlated with unesterified cholesterol levels. For women, pigs and rabbits (atherosclerosis-susceptible species) acyltransfer rate was significantly correlated with triacylglycerol and apolipoprotein B-linked cholesterol levels, but not with high desnity lipoprotein-cholesterol. In contrast, acyltransfer rates for rats and bovines (atherosclerosis-resistant species) were significantly correlated with high density lipoprotein-cholesterol, but not with the other parameters. These results, together with the corresponding partial correlation analyses, suggest significant functional differences for lecithin:cholesterol acyltransfer in atherosclerosis-resistant and athrosclerosis-susceptible species and that in the latter group, this enzyme may be mainly invilved in the disposal of cholesterol from triacylglycerol-rich lipo-proteins rather than in removing excess tissue cholesterol for transport to the liver

Alterations in the fatty acyl composition of plasma cholesteryl esters in brazilian patients with hepatosplenic schistosomiasis mansoni

1. The dyslipoproteinemia commonly occurring in the hepatosplenic forms of schistosomiais mansoni in Brazilian patients is characterized by low plasma levels of choleteryl esters and of the cholesterol-esterifying enzyme, lecithin:cholesterol acyltransferase (LCATase, EC.2.3.1.43). 2. In the present study, normal helathy individual and patients sufferin from hepatosplenic schistosomiasis mansoni were comapred for the fatty acyl compositons of circulating plasma cholesteryl esters and of those formed in vitro by the action of LCATase on a) the endogenous plasma lipoprotins and b) an excess of lipoprotein substrate composed of heat-inactivated plasma. 3. In patient palsma the proportions of saturated and monounsaturated cholesteryl esters were higher and those of diunsaturated and polyunsaturated esters were lower than in the control group. 4. Similar differences were observed between patients and controls in the proportions of the cholesteryl ester subclasses formed in vitro by the action of LCATase on endogenous plasma lipoprotins. 5. Incubation of fresh normal or patient plasma with escess heat-inactivated plasma as substrate for LCATase produced proportions of cholesteryl ester subclasses similar to those formed dduring incubation of nonheated aliquots of the appropriate plasma. 6. We conclude that the alterations in fatty acyl composition of palsma cholesteryl estes in patients with hepatosplenic schistosomiasis mansoni do not appear to be direct consequence of the low levels of LCATase acivity in patient plasma