Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.

Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice.

Statins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional changes on hepatocyte mitochondria. In a mouse model we studied the combined administration of a cholesterol-rich diet along with mild and moderate doses of rosuvastatin (1, 2.5 or 5 mg/kg/day) during several days. After the animals were sacrificed, liver mitochondria were isolated for microscopic studies and to analyze the respiratory function. The respiratory control (state-3/state-4) was evaluated in mice who received high doses of rosuvastatin. Rosuvastatin doses higher than 20 mg/kg/day induced premature death in mice with a hypercholesterolemic diet, but not in mice with a cholesterol-free diet. Doses from 2.5 to 5 mg/kg/day also induced morphological and functional alterations in mitochondria but these hypercholesterolemic animals survived longer. Giving 1 mg/kg/day, which is close to the maximal therapeutic dose for humans, did not affect mitochondrial architecture or respiratory function after two months of treatment. We analyzed the effect of rosuvastatin on hepatic tissue because it is where statins are mainly accumulated and it is the main site of endogenous cholesterol synthesis. Our results contribute to understand the side effects of rosuvastatin in hypercholesterolemic mice, effects that could also affect humans who are intolerant to statins.

Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia.

Obesity is the major risk factor for several cardiovascular and metabolic disorders. Previous studies reported that deletion of Angiotensin II type 2 receptor (AT2R) protects against metabolic dysfunctions induced by high fat (HF) diet. However, the role of AT2R in obesity-induced cardiac hypertrophy remains unclear. Male AT2R knockout (AT2RKO) and wild type (AT2RWT) mice were fed with control or HF diet for 10 weeks. HF diet increased cardiac expression of AT2R in obese mice. Deletion of AT2R did not affect body weight gain, glucose intolerance and fat mass gain induced by HF feeding. However, loss of AT2R prevented HF diet-induced hypercholesterolemia and cardiac remodeling. Mechanistically, we found that pharmacological inhibition or knockdown of AT2R prevented leptin-induced cardiomyocyte hypertrophy in vitro. Collectively, our results suggest that AT2R is involved in obesity-induced cardiac hypertrophy.

Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction.

AIMS: We previously demonstrated that iron overload induces endothelial dysfunction and oxidative stress, which could increase the risk for atherosclerosis. However, the iron-related harmfulness under a genetic predisposition to atherosclerosis is still unclear. Here, we have tested the hypothesis that chronic iron overload may change vascular reactivity associated with worsening of the atherosclerotic process in apolipoprotein E knockout (apoE(-/-)) mice. MAIN METHODS: Serum and aortas of wild-type (WT) and apoE(-/-) mice injected with iron-dextran (IO, 10 mg/mouse/day, ip) or saline 5 times a week for 4 weeks, were used. KEY FINDINGS: Iron overload increased serum levels of iron and biomarkers of liver injury and oxidative stress, and iron deposition in the aorta in both lines, but only apoE(-/-) IO mice had intensified hypercholesterolemia and atherosclerosis. By scanning electron microscopy, the small endothelial structural damage caused by iron in WT was worsened in the apoE(-/-) group. However, endothelial dysfunction was found only in the apoE(-/-) IO group, identified by impaired relaxation to acetylcholine and hyperreactivity to phenylephrine associated with reduced nitric oxide modulation. Moreover, tiron and indomethacin attenuated reactivity to phenylephrine with greater magnitude in aortas of the apoE(-/-) IO group. Confirming, there were changes in the antioxidant (superoxide dismutase and catalase) activity, increased expression of cyclooxygenase-2 in the aorta and elevated levels of thromboxane A2 and prostacyclin metabolites in the urine of apoE(-/-) IO. SIGNIFICANCE: Our results showed that chronic iron overload intensifies the atherosclerotic process and induces endothelial dysfunction in atherosclerotic mice, probably due to the oxidative stress and the imbalance between the relaxing and contractile factors synthesized by the damaged endothelium.

Behavioural, metabolic and neurochemical effects of environmental enrichment in high-fat cholesterol-enriched diet-fed mice.

While chronic high-fat feeding has long been associated with the rising incidence of obesity/type 2 diabetes, recent evidence has established that it is also associated with deficits in hippocampus-dependent memory. In this regard, environmental enrichment (EE) is an animal housing technique composed of increased space, physical activity, and social interactions, which in turn increases sensory, cognitive, motor, and social stimulation. EE leads to improved cerebral health as defined by increased neurogenesis, enhanced learning and memory and resistance to external cerebral insults. In the present study, the impacts of environmental enrichment (EE) on Swiss mice fed a high-fat, cholesterol-enriched diet (HFECD; 20% fat and 1.5% cholesterol) were investigated. Here, we demonstrated that EE, when initiated 4 weeks after the beginning of HFECD in mice, prevents HFECD-induced spatial memory and object recognition impairment, which were tested in T-maze and object recognition tests. Although EE did not affect HFECD-induced weight gain or hypercholesterolaemia, it improved glucose tolerance. On the other hand, EE was unable to mitigate a decrease in brain-derived neurotrophic factor (BDNF) and IL-6 hippocampal levels induced by the HFECD. Overall, while our results reinforce the positive and neuroprotective effects of EE on cognition they do not support a role for EE in preventing the neurochemical changes induced by the HFECD. Based on clinical observations that nondiabetic individuals with mild forms of impaired glucose tolerance have a higher risk of cognitive impairments, one can speculate about the connection between the effects of EE on glucose intolerance and its effects on cognition.

Cholesterol-Lowering and Liver-Protective Effects of Cooked and Germinated Mung Beans (Vigna radiata L.).

We investigated the hypocholesterolemic and liver-protective effects of cooked and germinated whole mung beans. Hamsters were fed for 28 days on diets rich in saturated fatty acids and cholesterol, differing only in protein source (20%): casein, cooked whole mung bean, and germinated mung bean. After 28 days, we found reduced plasma concentrations of total cholesterol and non-HDL cholesterol, increased faecal cholesterol excretion, and reduced levels of asparagine aminotransferase and alanine aminotransferase enzymes in the liver. Reduction in hepatic lipid deposition was observed between each of the mung bean groups relative to the casein group. In addition, the animals of the geminated mung bean group showed a lack of inflammatory infiltrate and better vascularisation of the hepatic tissue. Results from this study show significant hypocholesterolemic and liver-protective properties of the mung bean, which are further enhanced after germination.

Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats.

Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE) against the damage induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

AGE-albumin enhances ABCA1 degradation by ubiquitin-proteasome and lysosomal pathways in macrophages.

BACKGROUND AND AIMS: Advanced glycation end products (AGEs) induce cellular oxidative/endoplasmic reticulum stress and inflammation. We investigated its underlying mechanisms for atherogenesis focusing on regulation of ABCA1 protein decay in macrophages. METHODS: The ABCA1 decay rate was evaluated in macrophages after treatment with LXR agonist and by incubation with control (C) or AGE-albumin concomitant or not with cycloheximide, MG-132, ammonium chloride and calpain inhibitors were utilized to inhibit, respectively, proteasome, lysosome and ABCA1 proteolysis at cell surface. ABCA1 was determined by immunoblot and the protein decay rate calculated along time by the slope of the linear regression. Ubiquitination level was determined in ABCA1 immunoprecipitated from whole cell lysate or bulk cell membrane. AGE effect was also analyzed in THP-1 cells transfected with siRNA-RAGE. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/MS. One-way ANOVA and Student t test were utilized to compare results. RESULTS: CML and PYR-albumin were higher in AGE-albumin as compared to C. AGE-albumin reduced ABCA1 in J774 and THP-1 macrophages (20-30%) and induced a higher ABCA1 ubiquitination and a faster protein decay rate that was dependent on the presence of AGE during the kinetics of measurement in the presence of cycloheximide. Proteasomal inhibition restored and lysosomal inhibition partially recovered ABCA1 in cells treated with AGE-albumin. Calpain inhibition was not able to rescue ABCA1. RAGE knockdown prevented the reduction in ABCA1 elicited by AGE. CONCLUSIONS: AGE-albumin diminishes ABCA1 by accelerating its degradation through the proteasomal and lysosomal systems. This may increase lipid accumulation in macrophages by diminishing cholesterol efflux via RAGE signaling contributing to atherosclerosis in diabetes mellitus.

Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI), a high-density lipoprotein (HDL) receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h) mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the general population.

Elevated cholesterol levels have a poor prognosis in a cholestasis scenario.

Cholestasis results from defective bile flow through the biliary ducts leading to the accumulation of bile acids (BAs) in hepatocytes and serum. It has been seen that cholestasis is associated with hypercholesterolemia, which is a prerequisite for gallstone formation and primary biliary cirrhosis, being some of the most common gastrointestinal disorders in Western societies. Cytotoxic BAs induce proinflammatory mediators, oxidative stress, and apoptosis in hepatocytes, whereas cytoprotective BAs prevent them; they can also modify the plasmatic membrane structure of cells or mitochondrial outer membrane properties as well as the distribution of cholesterol, altering various proteins involved in BAs homeostasis.

Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice.

Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and ß-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds showing hypocholesterolemic properties and prebiotic effects.

Chronic use of pravastatin reduces insulin exocytosis and increases ß-cell death in hypercholesterolemic mice.

We have previously demonstrated that hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice secrete less insulin than wild-type mice. Removing cholesterol from isolated islets using methyl-beta-cyclodextrin reversed this defect. In this study, we hypothesized that in vivo treatment of LDLr(-/-) mice with the HMGCoA reductase inhibitor pravastatin would improve glucose-stimulated insulin secretion. Female LDLr(-/-) mice were treated with pravastatin (400mg/L) for 1-3 months. Isolated pancreatic islets were assayed for insulin secretion rates, intracellular calcium oscillations, cholesterol levels, NAD(P)H and SNARE protein levels, apoptosis indicators and lipidomic profile. Two months pravastatin treatment reduced cholesterol levels in plasma, liver and islets by 35%, 25% and 50%, respectively. Contrary to our hypothesis, pravastatin treatment increased fasting and fed plasma levels of glucose and decreased markedly (40%) fed plasma levels of insulin. In addition, ex vivo glucose stimulated insulin secretion was significantly reduced after two and three months (36-48%, p<0.05) of pravastatin treatment. Although reducing insulin secretion and insulinemia, two months pravastatin treatment did not affect glucose tolerance because it improved global insulin sensitivity. Pravastatin induced islet dysfunction was associated with marked reductions of exocytosis-related SNARE proteins (SNAP25, Syntaxin 1A, VAMP2) and increased apoptosis markers (Bax/Bcl2 protein ratio, cleaved caspase-3 and lower NAD(P)H production rates) observed in pancreatic islets from treated mice. In addition, several oxidized phospholipids, tri- and diacylglycerols and the proapoptotic lipid molecule ceramide were identified as markers of pravastatin-treated islets. Cell death and oxidative stress (H2O2 production) were confirmed in insulin secreting INS-1E cells treated with pravastatin. These results indicate that chronic treatment with pravastatin impairs the insulin exocytosis machinery and increases ß-cell death. These findings suggest that prolonged use of statins may have a diabetogenic effect.

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia.

Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4 in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.

Early onset intrauterine growth restriction in a mouse model of gestational hypercholesterolemia and atherosclerosis.

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22-24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.

Effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits.

The aim of the present study was to evaluate the effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. New Zealand male albino rabbits (n 21) were divided into two groups: group 1 (G1; n 11), fed a hypercholesterolaemic diet, and group 2 (G2; n 10), fed a hypercholesterolaemic diet enriched with flaxseed flour. The serum concentrations of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol, TAG and fasting blood glucose were determined at the start of the experiment and on the day of killing (8th week). Choroid and sclera samples were subjected to haematoxylin-eosin (HE) staining and histomorphometric and immunohistochemical analyses with the anti-oxidised LDL antibody. Sensory retina samples were subjected to an immunohistochemical analysis with the primary monoclonal nitrotyrosine antibody. At the end of the experiment, a significant increase was observed in TC and LDL-C concentrations in G1 rabbits when compared with G2 rabbits (P= 0·008 and P= 0·02, respectively). HE staining revealed a significant increase in choroid-sclera complex thickness in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of choroid and sclera samples with the anti-oxidised LDL marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of sensory retina samples with the anti-nitrotyrosine marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P= 0·002). Flaxseed reduced the choroid-sclera complex thickness of diet-induced hypercholesterolaemic rabbits and the expression of oxidised LDL in the choroid-sclera complex as well as the expression of nitrotyrosine in the sensory retina.

Influence of paeoniflorin on intracellular calcium ion concentration in the sphincter of Oddi of hypercholesterolemic rabbits.

This study aimed to investigate the influence of hypercholesterolemia (HC) on intracellular calcium ion concentration in the sphincter of Oddi (SO) of rabbits and the influence of paeoniflorin on intracellular calcium ion concentration in the hypercholesterolemic rabbit SO. Sixteen purebred New Zealand rabbits were randomly divided into two groups: the control group and the HC model group (8 rabbits in each group). The control group was fed standard diet. The HC group was fed standard diet plus cholesterol for a total of 8 weeks to induce and establish the rabbit HC model. The SO segment of HC rabbits was taken and enzyme treated to obtain SO cells. After primary culture, immunohistochemical analysis was performed. Fluo-3/AM was used to load SO cells, and then intracellular calcium ion concentration was determined by confocal microscopy. Intracellular calcium ion in the SO of the HC group was higher than that of the normal group; intracellular calcium ion in the HC rabbit SO of the paeoniflorin group was lower than that of the control group, where the paeoniflorin effect was greater with higher concentrations. High cholesterol caused an increase in intracellular calcium ion concentration in the rabbit SO, and paeoniflorin can reduce intracellular calcium ion concentration in the HC rabbit SO in a concentration-dependent manner.

Effects of atorvastatin in combination with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia.

The aim of this study was to observe the effects of atorvastatin combined with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia. A total of 84 elderly hypercholesterolemic patients complicated with carotid atherosclerosis were divided into control group (atorvastatin alone) and combined group (atorvastatin combined with ezetimibe) and treated for 12 months. Carotid atherosclerosis-related indicators including blood lipid and high-sensitivity C-reactive protein (hsCRP) were determined before and after treatment. The levels of carotid intima-media thickness (CIMT), serum low density lipoprotein cholesterol (LDL-C) and hsCRP were markedly decreased (P < 0.05) after treatment in the two groups, while the reduction of the levels of CIMT, serum LDL-C and hsCRP was more significant in the combined group (P < 0.01). After treatment, the levels of CIMT, serum LDL-C and hsCRP were distinctly different between combined and control group (P < 0.05). The combination of atorvastatin with ezetimibe could further decrease LDL-C and hsCRP levels and have certain effects on the progression of carotid atherosclerosis in elderly patients with hypercholesterolemia.

Avaliação dos fatores que caracterizam a berinjela (Solanum melongena L. ) como um alimento funcional / Evaluation factors featuring eggplant (Solanum melongena L. ) as a functional food

Currently, the role of healthy food is to optimize the nutrition of individuals, providing not only increased health and well-being, but also reduced risks of developing diseases caused by poor diets. Functional foods contain substances with different biological functions, called bioactive compounds, which can modulate the physiology of the body, ensuring the maintenance of health. Eggplant (Solanum melongena L.) has been cited by several authors as one of the vegetables that can be classified as functional food. The lay population has used eggplant in different ways, without criteria and evidence from studies with different objectives. Among its main uses, the treatment and/or prevention of dyslipidemia and as adjuvant in weight loss can be highlighted. This work aims to study and analyze the most recent publications in order to justify the characterization of eggplant (Solanum melongena L.) as a functional food. To this end, a literature review of articles was conducted in the Scielo, Medline, Pubmed, Bireme, and Lilacs databases, as well as in books and journals from 1992 to 2012. The selection of bibliographic reference sought to select studies that investigated the chemical composition of eggplant, elucidated its habitual use by populations, and attempted to demonstrate its functional properties. Although some studies have demonstrated the effectiveness of eggplant, more accurate investigations with standardized methodologies are needed. These further studies should address the usual forms of consumption by the population and the correlation of these forms with the objectives of the proposed use.

Actualmente, el papel de la alimentación considerada saludable es el de optimizar la nutrición de las personas, garantizándoles el aumento de la salud y del bienestar, al mismo tiempo que reduce el riesgo de desarrollar enfermedades causadas por la mala alimentación. Los alimentos funcionales presentan sustancias, denominadas compuestos bioactivos, que tienen diferentes funciones biológicas y que son capaces de modular la fisiología del organismo, garantizando el mantenimiento de la salud. La berenjena (Solanum melongena L.) ha sido citada por muchos autores como una de las hortalizas que se puede clasificar como alimento funcional. La berenjena ha sido utilizada por la población de diversas formas, aunque sin evidencias ni pruebas que lo respalden, y con diversos objetivos, entre los que podemos destacar el tratamiento y/o prevención de la dislipidemia y el auxilio en el adelgazamiento. Este trabajo tiene como objetivo estudiar y analizar las publicaciones más recientes que justifiquen la clasificación de la berenjena (Solanum melongena L.) como un alimento funcional. Para la estructuración de este estudio se realizó una revisión bibliográfica de artículos en las bases de datos Scielo, Medline, Pubmed, Bireme, Lilacs, así como en libros y revistas científicas, teniendo en cuenta el período de 1992 a 2012. La selección de la referencia bibliográfica intentó seleccionar aquellos estudios que investigaron la composición química de la berenjena, dilucidaron su uso habitual en las poblaciones y trataron de demostrar sus propiedades funcionales. Aunque algunos estudios han demostrado la eficacia de la berenjena, se necesitan investigaciones más precisas, con metodologías estandarizadas, que tengan en cuenta las formas habituales de consumo y las relacionen con los objetivos propuestos para su uso.

Atualmente o papel da alimentação considerada saudável é otimizar a nutrição dos indivíduos garantindo a estes o aumento da saúde e do bem-estar como também reduzir o risco de desenvolver doenças decorrentes da má alimentação. Os alimentos funcionais apresentam substâncias com distintas funções biológicas, denominadas compostos bioativos, que são capazes de modular a fisiologia do organismo, garantindo a manutenção da saúde. A berinjela (Solanum melongena L.) tem sido citada por diversos autores como um dos vegetais que podem ser classificados como alimento funcional. A utilização da berinjela vem sendo feita pela população leiga sob diversas formas, mesmo sem critérios e comprovações por estudos com objetivos diversos, entre eles destaca-se sua utilização para o tratamento e/ou prevenção da dislipidemia e também como coadjuvante na perda de peso. Este trabalho tem como objetivo estudar e analisar as publicações mais recentes que justifiquem a caracterização da berinjela (Solanum melongena L.) como um alimento funcional. Para a estruturação deste estudo, foi realizada uma revisão da literatura em artigos nas bases de dados Scielo, Medline, Pubmed, Bireme, Lilacs bem como em livros e revistas científicas, considerando o período de 1992 a 2012. A seleção da referência bibliográfica preocupou-se em selecionar os estudos que pesquisaram a composição química da berinjela, elucidaram seu uso habitual nas populações, bem como tentaram demonstrar suas propriedades funcionais. Apesar de alguns estudos demonstrarem a eficácia da berinjela, são necessárias investigações mais precisas, com metodologias padronizadas, realizadas com as formas habituais de consumo entre a população e relacioná-las com os objetivos propostos do seu uso.

[Increased VEGFR-1 immunoreactivity in the choroid-scleral complex in hypercholesterolemia experimental model]. / Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia.

PURPOSE: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the choroid and sclera using hypercholesterolemia experimental model. METHODS: New Zealand rabbits were divided into two groups: 8 rabbits (8 eyes), in the normal diet group (NG), were fed by a standard diet for 4 weeks; and 13 rabbits (13 eyes), in the hypercholesterolemic group (HG), were fed by a 1% cholesterol-enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the initiation of the experiment and at the euthanasia time. After hypercholesterolemic group 8th week and NG 4th week, animals were euthanized and their eyes underwent immunohistochemical analysis with the RAM-11 and VEGFR-1). RESULTS: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). There was a significant increase in the RAM-11 and VEGFR-1 expressions in hypercholesterolemic group choroid and sclera in relation to NG (p<0,001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the macrophage concentration and immunoreactivity to VEGFR-1 in the choroid and sclera, resembling human age-related macular degeneration (ARMD).