Allium sativum compared to cilostazol as an inhibitor of myointimal hyperplasia

Abstract Objective: Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods: Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results: Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion: We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

Estresse oxidativo e a função endotelial: efeitos do exercício físico associado à lipemia pós-prandial / Oxidative stress and endothelial function: effects of physical exercise on results of postprandial lipemia

Estratégias que possam prevenir o aparecimento da aterosclerose são de extrema importância para a saúde pública. O aumento da lipemia pós-prandial tem sido investigado, dentre os fatores de risco modificáveis para o desenvolvimento dessa doença, pois pode induzir dano oxidativo e disfunção endotelial. Nesse sentido, o exercício físico é indicado na prevenção do desenvolvimento desses fatores de risco. Esta revisão tem como objetivo realizar um levantamento e comparar os estudos publicados na literatura acerca dos efeitos agudos e subagudos do exercício físico associado à lipemia pós-prandial sobre o estresse oxidativo e a função endotelial. A busca foi realizada nos idiomas português, espanhol e inglês, compreendendo trabalhos publicados até fevereiro de 2015. Com base nos estudos selecionados, conclui-se que os efeitos agudos e subagudos do exercício físico podem ser capazes de atenuar os parâmetros de risco cardiovascular após o consumo de refeição hiperlipídica.

It is extremely important for public health to identify strategies that can prevent development of atherosclerosis. There are several modifiable metabolic risks that can induce onset of this disease, but the most investigated of these risk is increased postprandial lipemia after a high fat meal because this factor can increase oxidative damage and endothelial dysfunction. Physical exercise is indicated for prevention of development of these risk factors. The objective of this study was to search the literature for published studies investigating the acute and subacute effects on oxidative stress and endothelial function of physical exercise associated with postprandial lipemia and compare their results. Articles published up to February 2015 in Portuguese, Spanish or English were included. After an extensive review, it was concluded that the acute and subacute effects of physical could be capable of attenuating parameters of cardiovascular risk after consumption of a high fat meal.

Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

El consumo de futas y hortalizas ayuda a prevenir el daño endotelial / Consumption of fruits and vegetables in the prevention of endothelial damage

The endothelium helps to maintain the normal structure and homeostasis of the vasculature. However, chronic exposure to cardiovascular (CV) risk factors causes endothelial dysfunction, a phenomenon that is characterized by inflammation, reduced bioavailability of nitric oxide (NO) and a prothrombotic state. Epidemiological studies have shown that regular consumption of fruits and vegetables reduces CV risk, which has caused interest in knowing the bioactive compounds and the mechanisms involved. Among the components that protect the endothelium are antioxidants (vitamin C, vitamin E and poly phenols) and polyunsaturated fatty acids. Vitamin C and E promote vasodilatation protecting NO by blocking the reactive oxygen species (ROS). Poly phenols improve endothelial function primarily by increasing levels of NO, and inhibition of angiogenesis and platelet activation. Diets rich in poly-unsaturated fatty acids have shown beneficial effects by reducing the gene expression of cyclooxygenase-2 and the expression of cell adhesion molecules. This review mainly highlights the current understanding of endothelial dysfunction and the protective effect of endothelial cells by bioactive components of fruits and vegetables.

El endotelio normal ayuda a mantener la estructura y la hemostasia vascular. Sin embargo, la exposición crónica a factores de riesgo cardiovascular (CV) produce disfunción endotelial, fenómeno que se caracteriza por inflamación, disminución en la biodisponibilidad de óxido nítrico (NO) y un estado protrombótico. Estudios epidemiológicos han demostrado que el consumo regular de frutas y hortalizas disminuye el riesgo CV, lo que ha causado interés en conocer los compuestos bioactivos y los mecanismos involucrados. Entre los componentes que protegen el endotelio se encuentran las moléculas antioxidantes (vitamina C, vitamina E y polifenoles) y ácidos grasos poliinsaturados. Las vitaminas C y E favorecen la vasodilatación protegiendo el NO al bloquear las especies reactivas del oxigeno (ROS). Los polifenoles mejoran la función endotelial principalmente por el aumento de los niveles de NO, y la inhibición de la angiogénesis y de la activación plaquetaria. Dietas ricas en ácidos grasos poliinsaturados han mostrado efectos beneficiosos, mediante la reducción de la expresión géni-ca de la ciclooxigenasa-2 y de la expresión de moléculas de adhesión celular. Esta revisión principalmente señala los conocimientos actuales de la disfunción endotelial y el efecto protector de las células endoteliales por componentes bioactivos de frutas y hortalizas.

Inhibición de la proteína de transferencia de ésteres de colesterol para el manejo de la enfermedad cardiovascular ateroesclerótica: el segundo acto "Una esperanza que renace" / Cholesteryl ester transfer protein inhibition in the management of atherosclerotic cardiovascular disease: second act "A rebirth of hope"

Despite the clinical use of statins to reduce serum levels of LDL cholesterol and treat atherosclerotic cardiovascular disease, a high proportion of patients remain at significant residual cardiovascular risk. In this context, low HDL cholesterol levels are an additional risk factor and intervention studies suggest that a fraction of the cardiovascular protection achieved with pharmacotherapy is explained specifically by the increase in serum levels of HDL cholesterol. Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) can induce a significant elevation in HDL cholesterol and, potentially, lead to better control of residual cardiovascular risk beyond the benefit demonstrated by statins. While the use of torcetrapib had unexpected side effects, dalcetrapib and anacetrapib are new CETP inhibitors with a better safety profile and are currently under study to evaluate their effects on vascular lesions and clinical events in patients at high cardiovascular risk. If these studies show positive findings, we will witness a new biomedical advance as significant as was the clinical.

Alto contenido de ácido linoleico conjugado (CLA) en leche y productos derivados al incorporar semillas de girasol a la dieta vacuna: implicaciones sobre el riesgo trombo/aterogénico / High conjugated linoleic acid (CLA) content in milk and dairy products using a dietary supplementation of sunflower seed in cows: thrombogenic/atherogenic risk issues

Con la finalidad de determinar el perfil de ácidos grasos y la composición química de productos lácteos enriquecidos con ácido linoleico conjugado (CLA) de manera natural, se elaboraron crema, mantequilla y grasa butírica con leche obtenida de vacas que recibieron una dieta control o suplementación con semilla de girasol en un 11.2%. El análisis químico incluyó el perfil de ácidos grasos,materia grasa, proteína y cenizas; en la leche se determinó además el contenido de lactosa. Se calcularon los índices de aterogenicidad (IA) y trombogenicidad (IT) en la leche y productos elaborados. Los resultados indicaron que los contenidos de grasa, proteína, lactosa y ceniza no fueron afectados por la incorporación de semilla de girasol en la dieta de los animales. El contenido promedio de CLA y ácidotrans vaccénico (TVA) expresados en g/100 g de lípidos totales fue, para los productos control, 0.54 y 1.6; mientras que para los productos ricos en CLA fueron 2 y 6.4, lo cual representa un incremento de cuatro veces. Además, en los productos ricos en CLA los IA e IT disminuyeron considerablemente (38.4 y 25% menos, respectivamente). Se observó que los perfiles de ácidos grasos no se modificaron durante el procesamiento, indicando que el CLA es un componente estable en los productos lácteos analizados. El uso de semilla de girasol en la dieta de las vacas, incrementa el contenido de CLA y TVA en los productos lácteos y disminuye el riesgo de enfermedades cardiovasculares en humanos sin afectar la proporción de los componentes mayoritarios.

High conjugated linoleic acid (CLA) content in milk and dairy products using a dietary supplementation of sunflower seed in cows. Thrombogenic/atherogenic risk issues. This studywas undertaken to determine the effect of dietary supplementation of sunflower seed in cows on the chemical composition of milk and dairy products. Cream, butter and butter oil were prepared from milk produced by cows fed a control diet (control products) or diet supplemented with 11.2% sunflour seed (CLA-rich products). Milk samples collected were determined for lactose. A sample of CLArich or control product was determined for fatty acid profile as well as fat, protein and ash contents. The index of atherogenicity (IA) and the index of thrombogenicity (IT) were also calculated. Results revealed that there was no effect of the inclusion of sunflower seed in the diet on the lactose content in milk and total fat, protein and ash contents in the dairy products. Average contents of conjugated linoleic acid (CLA) and transvaccenic acid (TVA), expressed as g/ 100g total fatty acid were 0.54 and 1.6, respectively in the control products, and 2 and 6.4, respectively in the CLA-rich products. The content of either CLA or TVA was approximately four fold higher in the latter products. Moreover, CLA-rich products showed considerably low IA and IT, which were, respectively, 38.4 and 25.0% less than those from control products. Fatty acid profiles were unaffected during processing, which demonstrates that CLA is a stable component in the dairy products analyzed. It was concluded that dietary supplementation of sunflower seed in cows increases the CLA and TVA contents in milk, which may contribute to the reduction of the risk of cardiovascular diseases in humans.

A importância da prevenção primordial do colesterol / The primordial cholesterol prevention importance

A dislipidemia pode aparecer já na infância. Um dos grandes problemas de saúde pública hoje é o desenvolvimento precoce da obesidade, o que os americanos chamam de "coach potato" (literalmente "batata do sofá"), caracterizando crianças e adolescentes que comem muito e erradamente e não fazem quaisquer atividades físicas, relata nesta entrevista o mestre e doutor em Saúde Pública pela USP e diretor da Divisão Clínica do Instituto Dante Pazzanese de Cardiologia, dr. Marcelo Chiara Bertolami. A modificação do estilo de vida é parte essencial no controle das dislipidemias e na prevenção cardiovascular, com a adoção de boa prática alimentar e de atividade física regular, entre outros fatores. Ele chama a atenção para a prevenção primordial da aterosclerose, ou seja, a prevenção do fator de risco antes de seu desenvolvimento nas pessoas. "O caminho para isso é a educação entre as crianças, evitando que elas venham a fumar, a comer erradamente, a se tornarem obesas e sedentárias", afirma o especialista.

Protective effect of ginger, Zingiber officinale Rosc on experimental atherosclerosis in rabbits.

The effects of air dried ginger powder (0.1g/kg body weight, po, for 75 days) were studied on experimentally induced atherosclerosis in rabbits by cholesterol feeding (0.3g/kg body weight, po). Cholesterol feeding for 75 days lead to distinct development of atheroma in the aorta and coronary arteriesof the rabbits and this was significantly inhibited by about 50% following ginger administration. There was distinct decrease in lipid peroxidation and enhancement of fibrinolytic activity in ginger treated animals. However, ginger did not lower blood lipidsto any significant extent. This distinct protection from the development of atherosclerosis by ginger is probably because of its free radical scavanging, prostaglandin inhibitory and fibri properties.

Prevenção primária e secundária da aterosclerose: perspectivas atuais e futuras / Primary and secondary prevention of atherosclerosis: actual and future perspectives

A confluência de fatores de risco cardiovascular contribui para o desenvolvimento da doença aterosclerótica e para a ocorrência de eventos cardiovasculares. Em certas situações, como na síndrome metabólica, que inclui a resistência à insulina, o diabetes e as dislipidemias, os danos celulares e vasculares são potencializados e acelerados. Níveis elevados de colesterol estão relacionados ao aumento da incidência de doença aterosclerótica desde o estudo de Framingham. Diversos outros estudos epidemiológicos, clínicos e experimentais confirmam estes achados e o modelo lipídico da doença aterosclerótica consagrou-se definitivament como um dos principais responsáveis pelo surgimento desta doença. Por outro lado, cerca de 40 por cento dos indivíduos portadores de doença aterosclerótica coronariana apresentam níveis normais ou discretamente aumentados de LDL colesterol. Nesse sentido, outros fatores de risco têm sido identificados e o seu reconhecimento e a sua abordagem poderão contribuir para reduzir a morbimortalidade cardiovascular. O conceito atual, portanto, visa combater e controlar ao mesmo tempo todas as condições eventualmente presentes, de forma a obter o máximo de benefícios em termos da redução do risco de eventos cardiovasculares. Nesse cenário, o tratamento farmacológico das dislipidemias representa um grande avanço na redução dos eventos clínicos relacionados à aterosclerose coronariana, cerebrovascular ou periférica.

O papel das estratégias de mudanças do estilo de vida para a redução de eventos ateroscleróticos / The role of lifestyle changes strategies for atherosclerotic events reduction

Neste artigo, a autora avalia as estratégias de mudança do estilo de vida para redução do risco de eventos cardiovasculares. Inicialmente, situa a doença ateroscierótíca (DAC) e seus principais eventos infarto do miocárdio e acidente vascular cerebral como as principais causas de morte no mundo ocidental, que aumentam anualmente, sendo considerada a doença ateroscierótica uma doença da vida moderna. Neste sentido, realiza ampla revisão bibliográfica mencionando as diretrizes e metas da Sociedade Brasileira de Cardiologia-Departamento de Aterosolerose. Em seguida, nas estratégias de mudança do estilo de vida, menciona o abandono do tabagismo, os benefícios terapêuticas da atividade física e a importância da dieta, apresentando amplos dados bibliográficos com referência à modificação do perfil lipídico e da função endotelial e suas aplicações clínicas. Na discussão, apresenta resultados favoráveis e outras publicações sobre a associação entre o exercício físico e o risco do desenvolvimento da DAC, comprovando a necessidade da promoção da atividade física como prioridade da saúde pública. Com relação à terapêutica dietética, salienta a importância das fibras (soluvéis e insolúveis) e suas fontes, bem como as recomendações das quantidades nos Estados Unidos da América do Norte. Menciona o mecanismo de ação das fibras e os dados epidemiológicos que relacionam sua ingestão com a diminuição da incidência de coronariopatias, bem como ações da fibra dietática sobre a redução dos níveis de lipídeos (colesterol) e também a importância das fibras na terapêutica das dislipidemias, sendo atualmente reconhecidas como alimentos funcionais.

Hiper-homocisteinemia na doença arterial periférica / Hyperhomocysteinemia in peripheral arterial disease

Estudos recentes indicam que um nível plasmático elevado de homocisteína é um fator de risco importante e prevalente para doença vascular aterosclerótica coronariana, cerebral e periférica. A homocisteína é um aminoácido sulfurado utilizado em diversas vias metabólicas. A hiper-homocisteinemia pode ser atribuída à ocorrência de defeitos genéticos de algumas enzimas do metabolismo da homocisteína ou a deficiências nutricionais das vitaminas B6, B12 e folato, ou pode, ainda, estar relacionada a outros fatores de risco para aterosclerose. Foram sugeridos alguns mecanismos biologicamente plausíveis de dano vascular causado pela hiper-homocisteinemia, em especial a oxidação das lipoproteínas de baixa densidade (LDL). Em contrapartida, diversos estudos demonstram que a suplementação de ácido fólico resulta em redução eficiente da concentração de homocisteína no plasma. Nesta revisão, serão abordados o metabolismo da homocisteína e sua relação com a doença arterial periférica, e serão discutidas as causas, os mecanismos patogênicos e as perspectivas de tratamento da hiper-homocisteinemia.

Lipoproteínas de alta densidad (HDL). ¿Un objetivo terapéutico en la prevención de la aterosclerosis? / High densiy lipooproteins (hdl). a therapeutic objective i the atheroscleerosis prevention?

Las lipoproteínas de alta densidad (HDL) son una familia de partículas que difieren en tamaño, densidad y composición química. La heterogeneidad de las HDL resulta de la velocidad de síntesis y de catabolismo de las partículas, y de la acción de enzimas y proteínas de transporte que las remodelan continuamente. Los bajos niveles de colesterol HDL correlacionan con un riesgo elevado de desarrollar enfermedad aterosclerosa coronaria. La disminución de las HDL afecta el transporte reverso de colesterol, que es la vía metabólica responsable de la remoción del colesterol excedente de la células periféricas y su transporte hacia el hígado para reciclarlo o eliminarlo. Las HDL poseen además propiedades antiinflamatorias, antioxidativas, antiagregatorias, anticoagulantes y profibrinolíticas in vitro . Algunas de estas propiedades potencialmente antiaterosclerosas, también se han puesto de manifiesto in vivo con infusiones de HDL. Estas evidencias, además de la protección que se logra en modelos animales genéticamente modificados, permite plantear a las HDL como un objetivo primario en la prevención de la aterosclerosis coronaria. Algunos estudios epidemiológicos han demostrado una reducción importante en el riesgo cardiovascular asociado a elevaciones del colesterol HDL, principalmente en prevención secundaria. En consecuencia, elevar las concentraciones de las HDL a través de medidas higiénicas como el ejercicio aeróbico, la pérdida de peso y eliminar el tabaquismo, es ampliamente recomendado para reducir el riesgo coronario. Cuando las medidas higiénicas fallan, la intervención farmacológica con niacina o fibratos debe ser considerada en ciertos pacientes con niveles bajos de HDL. Por último, las diferentes subclases de HDL no poseen las mismas propiedades antiaterogénicas, lo que sugiere que las intervenciones tanto higiénicas como farmacológicas se deberán enfocar en el futuro hacia incrementos de la funcionalidad de las HDL, más que a incremento en la concentración del colesterol HDL.

High density lipoproteins (HDL) are a family of heterogeneous particles that vary in size, density and chemical composition, as a result of their synthesis and catabolism rates, and a continuous intravascular remodeling by the action of enzymes and transport proteins. Low plasma levels of HDL correlate with a high risk of atherosclerotic heart disease. Such a diminished concentration of HDL affect reverse cholesterol transport, which is the metabolic pathway responsible for the movement of cholesterol excess from peripheral tissues to the liver for recycling or excretion. In addition, HDL possess anti-inflammatory, anti-oxidative, anti-aggregatory, anti-coagulant, and pro-fibrinolytic properties, as has been demonstrated by in vitro studies. Some of those potentially anti-atherosclerotic in vitro-properties has been corroborated by HDL infusion in vivo. Such evidences and the protection of susceptible animals from atherosclerosis by transgenic manipulation of HDL metabolism, raise the possibility to focus the HDL plasma levels as a main target in coronary hearth disease prevention. Intervention trials have shown an important reduction in coronary events by rising HDL-cholesterol, mainly in the secondary prevention. Increasing HDL plasma levels by hygienic intervention such as aerobic exercise, weight loss and stop smoking is strongly recommended to reduce coronary risk in primary prevention. Pharmacological intervention to rise the HDL plasma levels with niacin or fibrates, should be considered in some patients as an alternative when hygienic intervention fails. Finally, it most be taken into account that the different HDL subclasses does not possess the same anti-atherosclerotic properties, suggesting that hygienic and pharmacological interventions should focus to increase HDL functionality rather than HDL-cholesterol plasma levels. (Arch Cardiol Mex 2004; 74:53-67).

Prevención / Prevention

El ser humano puede o no ser portador de factores de riesgo de enfermedad arterial. Los portadores, a su vez, pueden o no haber padecido episodios agudos de aterotrombosis. Los que no han padecido tales eventos pueden tener un factor o varios. Para esta gama de situaciones, existen estrategias de abordeje, particulares con puntos comunes. La prevención es prioritaria, especialmente la primaria, dirigida a los sin FREA: niños en particular. Se ha demostrado un comienzo temprano de la enfermedad por lo que la educación a los mismos es fundamental y debe extenderse a todos los grupos etarios. En algunas circunstancias también a temprana edad, es aconsejable la investigación clínica o por laboratorio de FREA, máxime en los con carga hereditaria. Las medidas comunes de dieta sana, sin tabaco, reducción de alcohol, incremento de la actividad física, se deberían incorporar en la sociedad como normas generales. En los ya portadores de FREA, en general adultos, es conveniente estabelecer el riesgo global o absoluto para considerar la profundidad del accionar médico y enfatizar adecuada adherencia a las indicaciones y prescripciones farmacológicas pertinentes. Para quéllos que ya han padecido un episodio agudo, la prevención secundaria implica constante consejería sobre los factores modificables, la prescripción de fármacos antigregantes plaquetarios y los que correspondan a cada factor individualmente. Existen tendencias modernas en el uso de hipolipemiantes, hipotensores y otros fármacos en prevención. Todos los componentes de la sociedad moderna deberían jugar un rol en las acciones de prevención.

Riesgo vascular global (primera parte) / Global vascular risk (first part)

En esta primera entrega de Evidencia se hace hincapié en el nuevo paradigma de evaluación del riesgo global para tomar decisiones en la prevención y el tratamiento de la enfermedad cardiovascular; se relativizan los conceptos de prevención primaria y secundaria; se describen datos epidemiológicos de Argentina así como la herramienta más difundida para la estimación del riesgo cardiovascular (el puntaje de Framingham) y se resume la principal evidencia que sustenta las intervenciones farmacológicas disponibles para el manejo de estos pacientes

Mechanism of action of antiatherogenic and related effects of Ficus bengalensis Linn. flavonoids in experimental animals.

One month treatment of alloxan diabetic dogs with a glycoside, viz. leucopelargonin derivative (100 mg/kg/day) isolated from the bark of F. bengalensis decreased fasting blood sugar and glycosylated haemoglobin by 34% and 28% respectively. Body weight was maintained in both the treated groups while the same was decreased significantly by 10% in the control group. In cholesterol diet fed rats, as the atherogenic index and the hepatic bile acid level and the faecal excretion of bile acids and neutral sterols increased, the HMGCoA reductase and lipogenic enzyme activities in liver and lipoprotien lipase activity in heart and adipose tissue and plasma LCAT activity and the incorporation of labelled acetate into free and ester cholesterol in liver decreased significantly. On treatment with the two ficus flavonoids, viz. leucopelargonin and leucocyanin derivatives and another flavonoid quercetin (100 mg/kg/day) the above said effects except on bile acids and sterols and lipogenic enzymes were significantly reversed in the cholesterol fed rats. However in the treated rats the hepatic level of bile acids and the faecal excretion of bile acids and neutral sterols still further increased and the action of lipogenic enzyme glucose 6 phosphate dehydrogenase was still further decreased. These effects of leucopelargonidin and quercetin were better than that of the second. Toxicity studies are required to be carried out to find out if the ficus flavonoids could be used as health promoters as they are hypocholesterolemic and antioxidant in action.