Associations Between Macronutrients From Different Dietary Sources and Serum Lipids in 24 639 UK Biobank Study Participants.

[Figure: see text].

The effect of aqueous extract of Lavandula officinalis to reduce cholesterol, triglyceride and other lipid metabolites on female BALB/c mice / Efecto del extracto acuoso de Lavandula officinalis en la reducción de colesterol, triglicéridos y otros metabolitos lipídicos en los ratones BALB/c hembra

BACKGROUND: Hyperlipidemia is a prevalent disorder and a main component of the metabolic syndrome resulting from various factors. The aerial parts and flowers of Lavandula officinalis possesses antioxidant activity, therefore, in this study; the effects of L. officinalis extract were investigated on serum lipid levels of mice. METHODS: Experimental mature female BALB/c mice were treated with 100, 300 or 500 mg/kg/day of lavender aqueous extract or distilled water for 15 days via intraperitoneally injections. At the end of 15th day, the serum biochemical parameters include cholesterol, triglyceride, HDL and LDL levels as well as the liver cell function test were determined. RESULTS: The aqueous extract of lavender significantly decreased serum cholesterol and LDL levels. Serum cholesterol level was lower in the 300 and 500 mg/kg/day experimental groups when compared with the control group. In liver histology evaluation, fat accumulation was not observed in the experimental group, which treated with high-fat foods and receiving high doses of extract. CONCLUSION: L. officinalis extract exerts a hypolipidemic effect in studied groups, however, further phytochemical and biological tests are suggested to determine the active chemical constituent responsible for these activities

ANTECEDENTES: La hiperlipidemia es un trastorno prevalente y un componente principal del síndrome metabólico originada por diversos factores. Las partes aéreas y flores de la Lavandula officinalis tienen una actividad antioxidante y, por tanto, investigamos en este estudio los efectos de su extracto en los niveles lipídicos séricos en ratones. MÉTODOS: Se trataron ratones BALB/c hembra maduras experimentales con 100, 300 o 500 mg/kg/día de extracto acuoso de lavanda o agua destilada durante 15 días, mediante inyecciones intraperitoneales. Al finalizar el 15.° día se investigaron los parámetros bioquímicos séricos incluyendo colesterol, triglicéridos, niveles de HDL y LDL, así como la prueba de la función hepática. RESULTADOS: El extracto acuoso de lavanda disminuyó significativamente los niveles séricos de colesterol y LDL. El nivel de colesterol sérico fue inferior en los grupos experimentales de 300 y 500 mg/kg/día, en comparación con el grupo control. En la evaluación de la histología hepática no se observó acumulación de grasa en el grupo experimental, que fue tratado con alimentos de alto contenido en grasa y recibió altas dosis de extracto. CONCLUSIÓN: El extracto de Lavandula officinalis ejerce un efecto hipolipidémico en el grupo estudiado, aunque son precisas más pruebas fitoquímicas y biológicas para determinar el constituyente químico activo responsable de estas actividades

Causas de no consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad en pacientes de alto y muy alto riesgo vascular controlados en Unidades de Lípidos y Riesgo Vascular. Estudio EROMOT / Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study

Objetivos: Determinar el grado de consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad (cLDL) en pacientes de alto y muy alto riesgo vascular atendidos en las unidades de lípidos, así como las causas de no consecución. Pacientes y método: Estudio observacional retrospectivo multicéntrico. Se incluyó a los pacientes mayores de 18 años con alto o muy alto riesgo vascular, según los criterios de la Guía europea de prevención cardiovascular de 2012, remitidos de forma consecutiva a las unidades de lípidos entre enero y junio del 2012 y con seguimiento a los 2 años de la primera visita. Resultados: Se incluyó a 243 pacientes procedentes de 16 unidades de lípidos. La edad media fue de 52,2 años (DE 13,7) con un 62,6% de varones. Un 40,3% eran de muy alto riesgo. En la primera visita seguían tratamiento hipolipidemiante el 86,8% (en combinación 25,1%) y en la segunda visita el 95,0% (en combinación 47,3%) (p<0,001). El 28% (IC del 95%: 22,4-34,1) alcanzó el objetivo terapéutico. Sobre las causas de no consecución, el 24,6% de ellas estaban relacionadas con el medicamento (10,3% máxima dosis tolerada y 10,9% por aparición de efectos adversos), el 43,4% con el médico (19,4% por inercia, 13,7% por considerar que ya ha llegado al objetivo) y con el paciente el 46,9%, destacando el incumplimiento terapéutico (31,4%). Conclusiones: Se consiguieron los objetivos de cLDL en cerca de un tercio de los pacientes. La baja adherencia del paciente, seguida de la inercia médica, son las causas más frecuentes que pueden explicar estos resultados (AU)

Objectives: Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. Patients and method: Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. Results: The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). Conclusions: LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results (AU)

LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma.

BACKGROUND: Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. METHODS: We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib. RESULTS: The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells. Furthermore, RCC xenograft tumours resist TKIs in mice fed a high-fat/high-cholesterol diet. CONCLUSIONS: The ability of renal tumours to maintain their cholesterol homoeostasis may be a critical component of TKI resistance in RCC patients.

Utilidad del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg frente a atorvastatina 80 mg en la reducción de los niveles de colesterol LDL en pacientes con ictus isquémico o ataque isquémico transitorio / Utility of treatment with atorvastatin 40 mg plus ezetimibe 10 mg versus atorvastatin 80 mg in reducing the levels of LDL cholesterol in patients with ischaemic stroke or transient ischaemic attack

Introducción. Tras un ictus isquémico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones más intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg más ezetimiba 10 mg tras un ictus isquémico o ataque isquémico transitorio (AIT). Pacientes y métodos. Evaluación de la eficacia del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificación de parámetros lipídicos tras un ictus isquémico o AIT. Se estableció como objetivo primario la obtención de niveles de LDLc ≤ 70 mg/dL o la reducción de las cifras de LDLc ≥ 50%. Adicionalmente se evaluó la presencia de efectos secundarios en ambos grupos. Resultados. Se observó un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg más ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg más ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p < 0,001), colesterol total (p = 0,001) y no HDLc (p < 0,001). Ambos tratamientos fueron seguros, con escaso número de efectos secundarios. Conclusiones. En comparación con atorvastatina 80 mg, el tratamiento con atorvastatina 40 mg más ezetimiba 10 mg incrementa la probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados (AU)

Introduction. After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. Aim. To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). Patients and methods. We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc ≤ 70 mg/dL and/or reduction in LDLc ≥ 50%. Furthermore, safety parameters were assessed. Results. Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. Conclusions. Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated (AU)

[Are treatments with statins that are considered unsuitable really unsuitable?]. / ¿Son realmente inadecuados los tratamientos con estatinas considerados como inadecuados?

In the Catalonian Institute of health there are 2 well-established circumstances for indicating lipid-lowering drug treatment with statins in the primary prevention of ischaemic heart disease. These are, severe hypercholesterolaemia, with a low density lipoprotein cholesterol equal to or greater than 240mg/dL, or above 130mg/dL when the coronary risk is equal to or greater than 10% at 10 years. There are data that suggest that these 2 criteria are not the only ones used in routine clinical practice, as such that the majority of patients to whom it is indicated, do not meet either of these 2 conditions. This study aims to determine the characteristics of the patients when statins are indicated outside the aforementioned circumstances. It is concluded that around 40% of patients have clinical characteristics that could justify the treatment. The level of suitability could not be established in about 33% of the patients, due to not being able to determine the coronary risk.

Meta-analysis methods and models with applications in evaluation of cholesterol-lowering drugs.

In this paper, we propose a class of multivariate random effects models allowing for the inclusion of study-level covariates to carry out meta-analyses. As existing algorithms for computing maximum likelihood estimates often converge poorly or may not converge at all when the random effects are multi-dimensional, we develop an efficient expectation-maximization algorithm for fitting multi-dimensional random effects regression models. In addition, we also develop a new methodology for carrying out variable selection with study-level covariates. We examine the performance of the proposed methodology via a simulation study. We apply the proposed methodology to analyze metadata from 26 studies involving statins as a monotherapy and in combination with ezetimibe. In particular, we compare the low-density lipoprotein cholesterol-lowering efficacy of monotherapy and combination therapy on two patient populations (naïve and non-naïve patients to statin monotherapy at baseline), controlling for aggregate covariates. The proposed methodology is quite general and can be applied in any meta-analysis setting for a wide range of scientific applications and therefore offers new analytic methods of clinical importance.

Consuming a diet complying with front-of-pack label criteria may reduce cholesterol levels: a modeling study.

BACKGROUND/OBJECTIVES: Front-of-pack nutrition labels can help consumers to make healthier choices and stimulate healthier product development. This is the first modeling study to investigate the potential impact on cholesterol levels of consuming a diet consisting of products that comply with the criteria for a 'healthier choice logo'. SUBJECTS/METHODS: National food consumption and food composition data were used to estimate the nutrient intake of the Dutch adult population (18-70 years) before and after replacing foods that did not comply with the choices front-of-pack label criteria. Different scenarios were established. The difference in cholesterol levels in the Dutch population was assessed before and after replacement by means of equations from meta-analyses that calculate how blood lipids change when diet composition changes. RESULTS: After replacing non-complying products with products, which comply with the label's criteria (maximum scenario), saturated fatty acids median intake reduced from 14.5 to 9.8 en%. Trans-fatty acids reduced from 0.95 to 0.57 en%. The average predicted changes in low-density lipoprotein and total cholesterol levels were -0.25 and -0.31 mmol/l, respectively. Because high-density lipoprotein (HDL) cholesterol levels reduced as well (-0.05 mmol/l), overall, the result was a slightly positive change in the total cholesterol/HDL ratio (-0.03). CONCLUSIONS: Our findings suggest that the consumption of foods complying with the criteria for a front-of-pack label could contribute moderately to cardiovascular risk reduction via influencing blood lipids. These findings were independent of other potential effects on related health outcomes.

Long time evolution of atherosclerotic plaques.

The evolution of atherosclerosis in general, and the influence of wall shear stress on the growth of atherosclerotic plaques in particular, is an intricate phenomenon which is still only partly understood. We therefore propose a qualitative mathematical model which consists of a number of ordinary differential equations for the concentrations of the most relevant constituents of the atherosclerotic plaque. These equations were studied both for the case that the wall shear stress is a parameter (model A), and for the case in which the plaque evolution is coupled to the blood flow (model B) which results in a time dependent wall shear stress. We find that both models exhibit a class of marginally stable equilibria, all reflecting states in which the plaque only grows for a short period of time after a perturbation. The uncoupled model A, however, shows bi-stability between this class of equilibria and another equilibrium state in which the plaque experiences unlimited growth in time, if the LDL cholesterol intake exceeds a threshold value. In model B the bi-stability vanishes, but we find that there is still a critical value of the LDL cholesterol intake beyond which the lumen radius drastically decreases. We show that this decrease is quite sensitive to the value of the wall shear stress.

Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL.

Epidemiological studies have linked statin use with a decreased risk of advanced prostate cancer and an improved recurrence-free survival after radical therapy. It is unclear, however, whether statins could have direct effects against prostate cancer in a clinical setting, as their growth-inhibiting effects on prostate cancer cells have been demonstrated at drug concentrations which exceed the level in plasma during standard clinical dosing. We compared responses to high-dose and therapeutic-dose simvastatin in normal and cancerous prostate epithelial cells. Simvastatin was more effective at inhibiting the growth of normal prostate epithelial cells than of cancer cells. At therapeutic 100 nM concentration simvastatin had a cytostatic effect on normal cells: apoptosis was only slightly induced, but a decrease in cell cycle activity and an increase in senescence were observed. At therapeutic concentrations, lipophilic simvastatin caused a stronger growth inhibition than did hydrophilic rosuvastatin. In contrast, 10 µM simvastatin had a cytotoxic effect both on normal and cancer cells. Addition of LDL-cholesterol effectively reversed the cytostatic effect in all cell lines, but overcoming the cytotoxicity of 10 µM simvastatin required a combination of LDL-cholesterol and mevalonate. As LDL-cholesterol completely prevented the growth-inhibiting effect of therapeutic-dose simvastatin already at low, subphysiological concentrations it is unlikely that statins have direct effects on growth of prostate epithelial cells in vivo. Statins' possible benefits against prostate cancer could be due to systemic cholesterol-lowering, as suggested by epidemiological studies. Future clinical studies evaluating the effects of statins on prostate cancer prevention should monitor serum LDL and should probably administer statins at higher concentrations than those currently used in the treatment of hypercholesterolemia.

Resistance training changes LDL metabolism in normolipidemic subjects: a study with a nanoemulsion mimetic of LDL.

OBJECTIVE: To evaluate the effects of resistance training (RT) on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism. METHODS: LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular RT for 1-4 years (age = 25 ± 5 years, VO(2)peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO(2)peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with (14)C-cholesteryl-ester and (3)H-free-cholesterol was injected intravenously, plasma samples were collected over 24-h to determine decay curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free-cholesterol, cholesteryl-ester, triacylglycerols and phospholipids. HDL size, paraoxonase-1 activity and oxidized LDL levels were also determined. RESULTS: The two groups showed similar LDL and HDL-cholesterol and triacylglycerols, but oxidized LDL was lower in RT (30 ± 9 vs. 61 ± 19 U/L, p = 0.0005). In RT, the nanoemulsion (14)C-cholesteryl-ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs. 0.037 ± 0.028, p = 0.002), as well as (3)H-free-cholesterol (0.041 ± 0.025 vs. 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, RT (3)H-free-cholesterol was removed slower than (14)C-cholesteryl-ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups. CONCLUSIONS: RT accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in RT. RT also changed the balance of free and esterified cholesterol FCR's. However, RT had no effect on HDL metabolism related parameters.

Exercise training accelerates the removal from plasma of LDL-like nanoemulsion in moderately hypercholesterolemic subjects.

OBJECTIVE: Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events. METHODS: Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with (14)C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24 h after injection to determine the fractional clearance rate (FCR, in h(-1)) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period. RESULTS: In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443+/-0.0126; 0.0602+/-0.0187, p=0.0187 and 0.0503+/-0.0203; 0.0686+/-0.0216, p=0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation. CONCLUSION: In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation.

Cholesterol, LDL, and 25-hydroxycholesterol regulate expression of the steroidogenic acute regulatory protein in microvascular endothelial cell line (bEnd.3).

The steroidogenic acute regulatory (StAR) protein promotes intramitochondrial delivery of cholesterol to the cholesterol side-chain cleavage system. In this experiment, we first demonstrated that StAR expressed in endothelial cells as well. Immunochemistry showed positive staining of StAR in endothelial cells. To investigate whether steroids and oxysterols regulate StAR expression in endothelial cells, mouse brain microvascular endothelial cell line (bEnd.3) was treated with various steroids and oxysterols, including free cholesterol (CHO), low density lipoprotein (LDL), and 25-hydroxycholesterol (25-OH). All these three compounds increased StAR mRNA and protein expression in a time- and dose-dependent manner. When treated with CHO and LDL, the StAR mRNA change was prior to the protein change, suggesting that transcription may be one of the mechanisms of CHO and LDL regulation. In contrast to CHO and LDL, 25-OH increased StAR protein levels independently of mRNA amount. It suggested that 25-OH might regulate StAR activity at post-transcriptional level.

Participación de la lipoproteína de baja densidad oxidada en el desarrollo de la placa aterosclerótica / The role played by oxidised low-density lipoprotein in the development of the atherosclerotic plaque

Objetivo. Exponer cuáles son los mecanismos por los cuales los lípidos plasmáticos, y concretamente la lipoproteína de baja densidad (LDL) oxidada, contribuyen al desarrollo de la placa ateromatosa. Desarrollo. La disfunción endotelial y la formación de la estría grasa constituyen la etapa inicial en el desarrollo de la arterioesclerosis. La hipercolesterolemia favorece la oxidación de LDL en contacto con radicales libres de oxígeno liberados por células endoteliales, macrófagos y células musculares lisas, y su captación y acumulación incontrolada por macrófagos subendoteliales, que se transforman en células espumosas. El acúmulo de estas células, con un leve engrosamiento intimal, constituye la estría grasa. La LDL oxidada estimula la quimiotaxis de células inflamatorias, su adhesión a células endoteliales y su migración al interior de la pared vascular; además, promueve la proliferación de células musculares lisas y su infiltración en el espacio subintimal; induce la apoptosis en el núcleo de la placa, favorece un estado protrombótico y reduce la función fibrinolítica. Así, participa en la progresión de las lesiones hacia placas ateromatosas bien estructuradas. La aplicación terapéutica de suplementos dietéticos de antioxidantes y –más importante en la actualidad– la administración de estatinas pueden retrasar la progresión de lesiones arterioescleróticas. Conclusiones. La hipercolesterolemia, a través de la LDL oxidada, ejerce un papel fundamental en el proceso de la aterogénesis. El conocimiento de su mecanismo de actuación es importante para el cirujano vascular, ya que supone una eficaz diana terapéutica

AIM. To present how plasma lipids, and particularly oxidized low-density lipoprotein (LDL), participate in the development of the atheromatous plaque. DEVELOPMENT. Endotelial dysfunction and the development of fatty streaks are the initial events in the process of plaque formation. Hypercholesterolemia favours the oxidation of LDL in contact with oxygen-derived free radicals released by endothelial cells, macrophages and smooth muscle cells, and their uncontrolled uptake and accumulation by subendothelial macrophages, which turn into foam cells. The accumulation of these cells, together with a slight intimal thickening, makes up the fatty streak. The oxidized LDL stimulates the chemoattraction of inflammatory cells, their adhesion to endothelial cells and their migration into the structure of the vascular wall. It promotes the proliferation of smooth muscle cells and their infiltration into the subintimal space. It induces cell apoptosis in the core of the plaque, and it favours a prothrombotic state by reducing the fibrinolytic activity. Thus, it participates in the progression of the vascular lesions towards well-structured atheromatous plaques. The therapeutic application of diet supplements of antioxidants or, more important nowadays, the prescription of statins, can slow down the progression of atherosclerotic lesions. CONCLUSIONS. Hypercholesterolemia, by means of the oxidized LDL, plays an essential role in the atherosclerotic development. It is important for the vascular surgeon to be familiar with this process because it is an effective therapeutic target

Dexamethasone impairs cholesterol egress from a localized lipoprotein depot in vivo.

Plasma high density lipoproteins play a central role in the prevention and regression of atherosclerosis, as they are known to promote egress of cholesterol from cells. Glucocorticoids increase plasma HDL, but enhance esterification of cholesterol in macrophages in vitro. A novel model to measure cholesterol egress from a well defined depot in vivo was used currently to study the effect of dexamethasone on reverse cholesterol transport. Cationized LDL (cat LDL) (200 microg cholesterol) was injected into the rectus femoris muscle of mice and the egress of cholesterol was studied as a function of time. Daily subcutaneous injection of dexamethasone (1.25 microg) raised plasma HDL levels by 40-80%. In mice injected with cat LDL labeled with 3H-cholesterol, daily treatment with dexamethasone slowed the loss of labeled cholesterol from the depot. With dexamethasone, there was no removal of the mass of lipoprotein cholesterol up to 14 days after injection of cat LDL, while in the controls 75% of the exogenous cholesterol mass had been cleared from the depot. When the cat LDL had been labeled with 3H-cholesteryl ester (3H-CE), apparent hydrolysis of 3H-CE amounted to 46, 75 and 97% in controls, but only to 20, 48 and 65% in dexamethasone treated mice on days 4, 8 and 14, respectively. In addition, dexamethasone stimulated cholesterol re-esterification as evidenced by recovery of 80% of the retained cholesterol mass as CE. In experiments with cultured macrophages exposed to modified LDL, dexamethasone increased the amount of labeled cholesteryl ester by 50-75% as compared to controls. Histological examination of the rectus femoris muscle after injection of cat LDL showed that in dexamethasone treated mice cellular infiltration was sparser on day 4, but not on day 8, and persisted longer than in controls. In conclusion, dexamethasone treatment impeded cholesterol egress from a lipoprotein depot by: a) reduction of early inflow of mononuclear cells; b) partial inhibition of cholesteryl ester hydrolysis, and c) enhancement of cholesterol esterification. The latter effect did not permit cholesterol egress from the injected site even in the presence of high plasma HDL in dexamethasone treated mice.

Estimulación del riesgo lipídico por niveles de colesterol sérico total / Appretiations of lipidic risk by total serum cholesterol

En 186 adultos sanos de Tucumán incluídos en la base de datos del Estudio de Factores de Riesgo en la Argentina SAC88, se clasificó al riesgo lipídico como: 1) normal: LDL100 mg/dl; 2) intermedio: LDL entre 100-150 mg/dl; 3) elevado: LDL >150mg/dl. Se distribuyó a la población de acuerdo a la colesterolemia como: <200,200-250,>250. Para discriminar la población normal se seleccionó la cifra <170. En cada grupo constituido se determinó la incidencia de la relación Col Tol/HDL anormal (ò 4,5). Existen una relación lineal entre concentraciones crecientes de colesterol total y los siguientes: 1) Incidencia de LDL a valores de riesgo lipídico elevado (coeficiente de 0,998); 2) incidencia en la población de un conciente Col Tol/HDL anormal (coeficiente de 0,999). Los incrementos en el LDL tienden a ser compensados por aumentos en HDL (p=0,05-0,10) pero tal compensación es ineficaz. En consecuencia, las cifras de colesterol total discriminan a la población con : 1) riesgo lipídico normal: colesterol <170 (especificidad 88,6 por ciento, sensibilidad 77,55); 2)riesgo lipídico elevado: colesterol >250 (especificidad 94,9 por ciento, sensibilidad 53,6 por ciento); 3) riesgo lipídico anormal: colesterol>200 (especificidad 98,2 por ciento, sensibilidad 73,3 por ciento), a valores de riesgo lipídico intermedio (35,8 por ciento) y elevado (62,4 por ciento)

Estimulación del riesgo lipídico por niveles de colesterol sérico total / Appretiations of lipidic risk by total serum cholesterol

En 186 adultos sanos de Tucumán incluídos en la base de datos del Estudio de Factores de Riesgo en la Argentina SAC'88, se clasificó al riesgo lipídico como: 1) normal: LDL100 mg/dl; 2) intermedio: LDL entre 100-150 mg/dl; 3) elevado: LDL >150mg/dl. Se distribuyó a la población de acuerdo a la colesterolemia como: <200,200-250,>250. Para discriminar la población normal se seleccionó la cifra <170. En cada grupo constituido se determinó la incidencia de la relación Col Tol/HDL anormal (ò 4,5). Existen una relación lineal entre concentraciones crecientes de colesterol total y los siguientes: 1) Incidencia de LDL a valores de riesgo lipídico elevado (coeficiente de 0,998); 2) incidencia en la población de un conciente Col Tol/HDL anormal (coeficiente de 0,999). Los incrementos en el LDL tienden a ser compensados por aumentos en HDL (p=0,05-0,10) pero tal compensación es ineficaz. En consecuencia, las cifras de colesterol total discriminan a la población con : 1) riesgo lipídico normal: colesterol <170 (especificidad 88,6 por ciento, sensibilidad 77,55); 2)riesgo lipídico elevado: colesterol >250 (especificidad 94,9 por ciento, sensibilidad 53,6 por ciento); 3) riesgo lipídico anormal: colesterol>200 (especificidad 98,2 por ciento, sensibilidad 73,3 por ciento), a valores de riesgo lipídico intermedio (35,8 por ciento) y elevado (62,4 por ciento)

Contribution of a risk factor clinic to lipid management in patients with coronary artery disease.

The progress of a cohort of 145 patients seen between June 1986 and June 1989 was reviewed. These patients had treatment prescribed by the clinic and had data recorded over serial visits; they allowed us to determine the contribution of the risk factor clinic. Eighty-six percent had coronary artery disease. Patients were given nutritional advice, partly in groups. In addition 61% were treated with drug therapy. Seventy-four percent had modified their diet before the clinic visit but only 32% received less than 30% of energy from fat; the number rose to 67% by discharge. Sixty-four percent had a body mass index of 25 or greater, falling to 53% at discharge. Mean total cholesterol of the 145 patients was 7.9, HDL cholesterol 1.06, and total:HDL cholesterol ratio 7.7 mmol/L. Changes with clinic management were: total cholesterol -19%, HDL cholesterol +11%, total:HDL cholesterol ratio -25%, LDL cholesterol -21%. Despite these changes, levels were less than optimal for patients with coronary arterial disease in at least 50% of patients at the time of discharge. Improved results can be achieved only with a more aggressive approach to drug therapy. Recent studies in patients with coronary disease provide strong support for such a change in management.

Cholesterol-rich LDL perfused at physiological LDL-cholesterol concentration induces platelet aggregation and PAF-acetylhydrolase activation.

The aim of this research was to perform an in vivo study on the relationships between lipid oxide (LP), platelet aggregation and PAF-acetylhydrolase in a model using perfusion of cholesterol-rich LDL media diluted to physiological LDL-cholesterol concentration. Normal rabbits were infused with LDL (d 1.025-1.063 g/ml) extracted from rabbits previously fed either with standard food (I-LDL group), 1% cholesterol food (II-LDL group) or 1% cholesterol plus probucol (IV-LDL group). CU2+ modified II-LDL was also infused (III-LDL group). After dilution as above, LP increased significantly in III- and II-LDL media. After perfusion, LP significantly increased in III- and II-LDL groups as compared to baseline values and to control. Compared to the I-LDL group, PAF-acetylhydrolase and platelet aggregation significantly increased in III- and II-LDL groups. These data indicate the property of cholesterol- rich LDL to activate PAF-acetylhydrolase and enhance platelet aggregation, even when perfused through a medium containing a physiological LDL-cholesterol concentration.