Is increased apolipoprotein B-A major factor enhancing the risk of coronary artery disease in type 2 diabetes?

OBJECTIVES: An association of Apolipoprotein B (Apo B) with coronary artery disease (CAD) independent of LDL cholesterol (LDLc) concentrations has been reported in white population. This analysis was taken up to study whether the higher CAD risk in Asian Indians with diabetes could be explained by possible alterations in Apo B and Apolipoprotein A1 (Apo A1) concentrations. METHODS: The study group consisted of four hundred and forty seven men aged > or = 25 years, 167 with CAD and 280 with no CAD, classified by coronary angiography. Plasma lipid profile including total cholesterol, LDLc, Apo A1 and Apo B were done. Glucose tolerance was evaluated in all. RESULTS: Age, BMI, Apo B, and Apo A1 were significantly associated with CAD in a multiple regression analysis. Hyper Apo B was more common than hyper LDLc in CAD (73.6% vs 20.4%, chi2 = 157, P < 0.001). Apo B concentrations were increased in diabetic subjects even in the presence of normal levels of LDLc and in the absence of CAD. CONCLUSIONS: The study has shown that the apolipoproteins B and A1 provide better information regarding the risk of CAD. Apo B abnormalities exist in large percentages of CAD subjects despite having normal levels of LDLc. Diabetes per se enhances the Apo B concentrations and this could probably be one of the mechanisms of accelerated CAD in diabetes. Hyper Apo B may be an index of CAD risk.

Effects of a monophasic pill containing 20 microg ethinylestradiol and 150 microg desogestrel on lipid metabolism in Thai women.

OBJECTIVES: To investigate the effects of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel (Mercilon) on lipid metabolism in Thai women. METHOD: The study was carried out at the Family Planning Clinic of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Twenty women of fertile age were enrolled and treated with the study oral contraceptives for 12 cycles. Lipid parameters were assessed before treatment and periodically during treatment. RESULTS: There was a significant increase in triglyceride, high desity lipoprotein-cholesterol, apolipoproteins AI and AII. No significant changes were found in total cholesterol, low density lipoprotein-cholesterol and apolipoprotein B. CONCLUSION: The effects of the oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel on lipid parameters in Thai women appear to be favorably beneficial.

Oxidation-dependent effects of oxidized LDL: proliferation or cell death

Oxidized low-density lipoprotein (oxLDL) induces a wide range of cellular responses to produce atherosclerotic lesion, but key factors determining the response are not understood. In this study, purified LDL was oxidized with copper sulfate, and its physical properties and the related biological responses were investigated. The average hydrodynamic diameter of the lightly oxidized LDL was approximately 25 nm and its Rf value relative to nLDL on agarose gel was between 1.0 and 1.25. The diameter of the extensively oxidized LDL was over 30 nm, the Rf value was over 2.0. A 24 h-exposure of resting RAW264.7 macrophage cells to 100 microg/ml of the lightly oxidized LDL induced proliferation and macrophage activation whereas the extensively oxidized LDL induced cell death at the same concentration. In contrast, 200 microg/ml of oxLDL caused cell death regardless of oxidation degree. Short incubation (4-6 h) of the highly oxidized LDL (100 microg/ml) also resulted in cell proliferation. OxLDL-induced cell death showed mixed characteristics of apoptosis and/or necrosis depending on the strength and duration of the insult. These results suggest that cellular responses induced by oxLDL be dependent on the oxidation degree, the duration of exposure, and the concentration of oxLDL. Copyright 2000 Academic Press.

Synthesis and secretion of lipoproteins by primary cultures of rat hepatocytes.

Synthesis and secretion of VLDL and LDL by primary cultures of rat hepatocytes maintained in serum free medium have been studied. A time-dependent increase found in the [3H]leucine labelled lipoproteins which floated at a density of 1.006 g/ml indicate the secretion of VLDL into the medium. That the hepatocytes also secrete. LDL is shown by floatation of [3H]leucine labelled lipoproteins by sequential centrifugation at a density range of 1.006-1.06 g/ml. Electrophoretic and immunoprecipitation analysis show that about 60% and 65% respectively of 3H-radioactivity is associated with apoB in the two fraction of lipoproteins. At about 12hr 70-75% lipoproteins in the culture medium is in the VLDL density range and 25-30% is in the LDL density range. Conversion of secreted VLDL to LDL has also been shown by incubating hepatocytes with pre-labelled lipoproteins when there is a decrease in the fraction of VLDL range with a corresponding increase in the fraction of the LDL density range. Addition of glycosaminoglycans such as hyaluronic acid, chondroitin sulphate, and heparin into the medium cause significant increase in the synthesis and secretion of [3H]apoB into the medium indicating a possible secretory control of apoB by local reuptake.

Apolipoproteins A-1 and B as predictors of angiographically assessed coronary artery disease.

Serum lipids, lipoproteins, apolipoproteins (A-1 and B) were determined in 225 patients with angiographic evidence of coronary artery disease (having abnormal coronary angiogram and positive exercise stress test), and 112 patients without any clinical and/or angiographic evidence of coronary artery disease. The variable with the strongest association with coronary artery disease was the ratio of apo B/A-1. Thus, the determination of apolipoproteins yielded complementary information in this case control study and warrants further study in a prospective setting.

Partículas lipoproteicas: concepto, aislamiento e implicancias clínicas / Lipoprotein particles: concept, isolation and clinical significance

La utilización de la cromatografía de afinidad con concanavalina A o de cromatografía de inmunoafinidad con anticuerpos anti apoB permite obtener dos grupos de lipoproteínas: las que contienen apoA y las que contienen apoB. El subfraccionamiento por cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoA permite obtener a su vez tres mayores partículas lipoproteicas: LP-A-I, LP-A-I:A-II y LP-A-II. El subfraccionamiento a través de inmunoprecipitación secuencial o cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoB permite obtener cinco mayores grupos de partículas: LP-B, LP-B:C, LP-B:E, LP-B:C:E y LP-A-II:B. La diferencia entre normo e hiperlipoproteinémicos sería el resultado de cambios cuantitativos (y no cualitativos) de las partículas lipoproteicas. En hipercolesterolémicos se destaca un aumento de LP-B en tanto que en hipertrigliceridémicos aumentan la LP-B-C y LP-B:C:E. Las drogas hipolipemiantes, independientemente de su mecanismo de acción, afectan en diferentes sentidos las concentraciones de las partículas lipoproteicas que contienen apoA y apoB. Bajas concentraciones de LP-A-I y elevadas de LP-B:C y LP-B:C:E se asocian con riesgo aterogénico

Efecto de las lipoproteínas ricas en triglicéridos sobre la relación entre C-LDL y Apo B determinada por EID en suero total: I. indicadores de riesgo para la enfermedad coronaria. Valores de Apo B/C-HDL / Effect the triglyceride rich lipoproteins upon the relation between C-LDL and Apo B determined by EID in total serum: I.rick indications of coronary disease. Values of Apo B/C-HDL

En este trabajo se determinaron los valores promedio, desviación estándar y percentilos para el cociente Apo B/C-HDL y, por otra parte, se analizó el efecto de las lipoproteínas ricas en triglicéridos sobre la relación entre C-LDL y Apo B, determinada por electroinmunodifusión en suero total. Se estudiaron 74 individuos de 20 y más años, aparentemente sanos. Para Apo B/C-HDL se obtuvo un valor medio de 2,16+0,78. El percentilo 50 fue 2,00, el percentilo 75 fue 2,60 y el percentilo 95 fue 3,60. Los individuos con Apo B/C-HDL>3,60 estarían en riesgo respecto de la aterosclerosis coronaria. La relación entre C-LDL y Apo B, es importante para la detección de sujetos con hiperapo B, la cual está fuertemente relacionada con la aterosclerosis coronaria. Utilizando los triglicéridos como estimadores de masa de las lipoproteínas ricas en triglicéridos, se halló que mientras TG<160 mg/dl la correlación entre Apo B y C-LDL fue r= +0,65,P <0,001. Un 86% de los pacientes con C-LDL entre 80 y 165 mg/dl tenían Apo B entre 55 y 120 mg/dl, mientras que un 12% tenían Apo B por encima de 120 mg/dl. En estos pacientes se puede suponer la presencia de hiperapo B en estas condiciones experimentales. Cuando TG>160 mg/dl, la correlación entre Apo B y C-LDL disminuye a r=+0,39,P<0,1. Un 21% de los pacientes con C-LDL entre 80 y 165 mg/dl tenían Apo B entre 55 y 120 mg/dl, pero un 79% tenían Apo B por encima de 120 mg/dl. En estas condiciones experimentales no se podrían discriminar los pacientes con hiperapo B.