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.

Efeitos do fragmento variável de cadeia única anti-LDL eletronegativa vetorizado em nanocápsulas na aterosclerose experimental / Effects of an anti-LDL(-) single chain fragment variable vectorized in nanocapsules in experimental atherosclerosis

As doenças cardiovasculares são a principal causa de mortalidade no mundo. A aterosclerose é a base fisiopatológica dessas doenças, sendo definida como um processo crônico-inflamatório multifatorial, resultando da interação de diferentes células como linfócitos, macrófagos, células endoteliais e células musculares lisas na parede arterial. A lipoproteína de baixa densidade eletronegativa [LDL(-)], uma subfração modificada da LDL nativa, desempenha um papel-chave na aterosclerose, uma vez que as modificações sofridas por esta partícula são capazes de induzir o acúmulo de ésteres de colesterol em macrófagos e a subsequente formação de células espumosas. O sistema imunológico é crucial no processo aterogênico e estratégias terapêuticas direcionadas à imunoregulação deste processo têm sido utilizadas como novas alternativas tanto na prevenção do desenvolvimento quanto da progressão desta doença. Dentre essas estratégias, destaca-se o uso de fragmentos de anticorpos como o scFv (do inglês, single chain fragment variable), que podem ainda estar conjugados a nanopartículas com o intuito de aumentar sua eficiência de ação no organismo. Diante do papel da LDL(-) na aterosclerose, este projeto objetivou avaliar os efeitos in vitro e in vivo de um sistema nanoestruturado contendo fragmentos scFv anti-LDL(-) derivatizados na superfície de nanocápsulas sobre macrófagos murinos e humanos primários e em camundongos knockout para o gene do receptor da LDL (Ldlr-/-) no desenvolvimento e na progressão dessa doença. Demonstrou-se que o tratamento de macrófagos com a formulação scFv anti-LDL(-)-MCMN-Zn diminuiu de forma significativa a captação de LDL(-), assim como a expressão de IL-1ß (mRNA e proteína) e MCP-1 (mRNA). Foi demonstrada a internalização da nanoformulação pelos macrófagos via diferentes mecanismos de endocitose, demonstrando seu potencial uso como carreador de fármacos. In vivo, a nanoformulação diminuiu de forma significativa a área da lesão aterosclerótica em camundongos Ldlr-/- submetidos à avaliação pela técnica de tomografia por emissão de pósitrons (do inglês, PET), utilizando o radiotraçador 18F-FDG (18F-desoxiglicose), associada à tomografia computadorizada (CT) com agente de contraste iodado, além da análise morfométrica das lesões no arco aórtico. O conjunto dos resultados obtidos evidenciou a ação ateroprotetora da formulação scFv anti-LDL(-)-MCMN-Zn, reforçando seu potencial como estratégia terapêutica na aterosclerose

Cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerosis is the pathophysiological basis of these diseases, defined as a chronic inflammatory multifactorial process, resulting from the interaction of several cells such as lymphocytes macrophages, endothelial cells and smooth muscle cells within the arterial wall. The electronegative low-density lipoprotein [LDL(-)], a modified subfraction of native LDL, plays a key role in atherosclerosis, since its modifications are capable of inducing the accumulation of cholesteryl esters in macrophages and the subsequent foam cells formation. The immune system is crucial in atherogenic process and therapeutic strategies directed to the immunoregulation of this process have been used as a new alternative in the prevention of the development as well as the progression of this disease. Among these strategies, it is the use of antibody fragments such as scFv (single chain fragment variable), which may be also conjugated to nanoparticles in order to increase their efficiency in the body. Given the role of LDL(-) in atherosclerosis, the aim of this project was to evaluate the in vitro and in vivo effects of a nanostructured system containing scFv anti-LDL(-) fragments derivatized on the surface of nanocapsules on murine and human primary macrophages and in the development and progression of the disease in LDL receptor knockout mice (Ldlr-/-). It was demonstrated that the treatment of macrophages with scFv anti-LDL(-)-MCMN-Zn formulation significantly decreases the uptake of LDL(-) and the expression IL-1ß (mRNA and protein) and MCP-1 (mRNA). Moreover, the internalization of the nanoformulation by macrophages through different endocytosis mechanisms was shown, demonstrating its potential use as a nanocarrier. In vivo, the nanoformulation decreased the area of atherosclerotic lesions in Ldlr-/- mice evaluated by positron emission tomography with 18F-FDG associated with computed tomography with iodinated contrast agent (PET/CT), besides the lesion morphometric analysis at the aortic arch Thus, these data provide evidence of the atheroprotection action of the ateroprotection action of the scFv anti-LDL(-)-MCMN-Zn formulation, suggesting its promising use as a therapeutic strategy for atherosclerosis

Representações sociais de educação em saúde em tempos de AIDS / Social representations of health education in a time of AIDS / Representaciones sociales de educación para la salud en la era del SIDA

Estudo qualitativo e descritivo, cujo objetivo foi identificar e analisar as representações sociais de educação em saúde à pessoa vivendo com HIV entre profissionais de saúde. Os cenários foram três serviços de atenção à DST/HIV/AIDS, em Belém-PA, Brasil, e 37 profissionais de saúde participaram da pesquisa. A coleta de dados deu-se em 2012-2013 por meio de entrevista em profundidade; a análise utilizou o software Alceste 4.10. Com base no conjunto dos resultados foi possível vislumbrar que a educação em saúde pode ser compreendida a partir de categorias: a configuração do agir educativo; as condições sine qua non: educação no trabalho e estrutura da unidade; o processo pedagógico. Conclui-se que as representações sociais configuram-se como orientação-informação para precaução-prevenção e revelam-se no movimento do agir persistente ao emergente, o que suscita uma educação em saúde permanente para se chegar à integralidade nos serviços.

This is a qualitative and descriptive study, which aimed at identifying and analyzing social representations of health education to HIV patients among health professionals. The setting included three healthcare DST/HIV/AIDS services in Belém-PA, Brazil, and 37 health professionals participated in the study. Data collection was conducted in 2012-2013 on the basis of in-depth interviews and analysis was made on Alceste 4.0 software. Final results indicated that health education can be comprehended in light of categories: educational action; sine qua non: education and training at work, and unit structure; teaching-learning process. Conclusions show that social representations are set as guidance-information for precaution-prevention and that they come forth along continuous and emerging action flow, bringing about permanent health education to ensure healthcare services in full.

Estudio cualitativo y descriptivo, que objetivó identificar y analizar las representaciones sociales de educación en salud a la persona viviendo con HIV entre profesionales de salud. Los escenarios fueron tres servicios de atendimiento al DST/HIV/ SIDA, en Belém-PA, Brasil, y 37 profesionales de salud participaran del estudio. La colecta de datos se dio en 2012-2013, por medio de entrevista en profundidad y el análisis utilizo el software Alceste 4.10. Con base en el conjunto de los resultados fue posible vislumbrar que la educación en salud puede ser comprendida a partir de categorías: la configuración del acto educativo; las condiciones sine qua non: educación en el trabajo y estructura de la unidad; el proceso pedagógico. Se concluye que las representaciones sociales se configuran como orientación-información para precaución-prevención y se revelan en el movimiento del acto persistente al emergente, lo que suscita una educación en salud permanente para llegarse a la integralidad en los servicios.

Effect of increased levels of adiponectin by administration of the adenovector rAAV2/1-Acrp30 on glucose, lipid metabolism and ultrastructure of the aorta in Goto–Kakizaki rats with arteriosclerosis.

Background. We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto–Kakizaki (GK) rats with arteriosclerosis. Methods. Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (1012 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. Results. Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p<0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. Conclusion. Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.

Hipertensión arterial: el factor de riesgo más importante para grosor íntima-media carotídeo elevado y placa carotídea en adultos de Santiago / Risk factors for a high carotid intima media thickness among healthy adults

Background: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. Aim: To determine attributable risk factors for a high CIMT among healthy adults. Material ana Methods: A sample of 1270 individuáis (636 males and 634 femóles) aged 44 ±11 years, was studied. Blood pressure, weight, height, lipidprofile and blood glucose were measured in all. CIMT and thepresence of atheroscleroticplaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. Results: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and thepresence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57 percent, respectively. Conclusions: In this sample, the main risk factor for a high CIMT was hypertension.

Pitfalls in the assessment of murine atherosclerosis: [review]

This review provides examples of the fact that different procedures for the measurement of atherosclerosis in mice may lead to interpretation of the extent of atherosclerosis having markedly different biological and clinical significance for humans: 1) aortic cholesterol measurement is highly sensitive for the detection of early and advanced atherosclerosis lesions, but misses the identification of the location and complexity of these lesions that are so critical for humans; 2) the histological analysis of the aortic root lesions in simvastatin-treated and control mice reveals similar lesion morphology in spite of the remarkable simvastatin-induced reduction of the aortic cholesteryl ester content; 3) in histological analyses, chemical fixation and inclusion may extract the tissue fat and also shrink and distort tissue structures. Thus, the method may be less sensitive for the detection of slight differences among the experimental groups, unless a more suitable procedure employing physical fixation with histological sample freezing using optimal cutting temperature and liquid nitrogen is employed. Thus, when measuring experimental atherosclerosis in mice, investigators should be aware of several previously unreported pitfalls regarding the extent, location and complexity of the arterial lesion that may not be suitable for extrapolation to human pathology.

Neoangiogenese na aterosclerose: modulacao por lipides nitrados / Neoangiogenesis in atherosclerosis: modulation through nitrated lipids

Lípides nitrados (NO₂-FA) são apontados como uma nova classe de mediadores lipídicos, podendo atuar como reservatórios endógenos de Oxido nítrico (^.NO) bem como moduladores pluripotentes de sinalização celular. Recentemente, tem sido sugerido que os doadores de ^.NO estariam envolvidos na regulação da angiogênese. Evidências contundentes indicam ainda que o processo de neovascularização poderia contribuir para a patogênese de uma serie de condições clínicas, entre elas a aterosclerose. Contudo, apesar de diversos estudos terem explorado os efeitos biológicos dos NO₂-FA, os efeitos destes compostos sobre o processo de angiogênese não haviam sido descritos. Dessa maneira, o presente trabalho investigou os efeitos dos NO₂-FA (derivados da nitração do acido linoléico e oléico) no processo de angiogênese. Demonstrou-se que os NO₂-FA podem atuar como mediadores pro-angiogênicos. Este efeito foi caracterizado em células endoteliais humanas, assim como, em modelos ex vivo e in vivo. Nas células endoteliais, observou-se que os NO₂-FA não influenciaram a proliferação ou a viabilidade celular, ao passo que estimularam a migração. Demonstrou-se também que os NO₂-FA podem modular o brotamento ex vivo de novos vasos, em cultura de anéis de aorta de rato, bem como o processo angiogênico in vivo observado na membrana corioalantóica de embrião de galinha. Adicionalmente, os NO₂-FA induziram a expressão do fator de crescimento endotelial vascular (VEGF), que é o principal mediador do processo de angiogênese. Em relação ao mecanismo de ação, os achados sugerem que os efeitos demonstrados seriam via mecanismos dependentes de ^.NO, uma vez que foram abolidos na presença de um seqüestrador de ^.NO, enquanto concentrações equivalentes dos Lípides precursores não demonstraram qualquer influência nas condições experimentais utilizadas neste estudo...

Nitrated lipids ( NO₂-FA) are described as a new class of lipid mediators that are able to act as endogenously nitric oxide ( ^.NO) reservoirs as well as pluripotent cell signaling modulators. Furthermore, recent findings suggest that ^.NO donors could be involved in the regulation of angiogenesis. Compelling evidence also indicate that the neovascularization process might contribute to the pathogenesis of many clinical conditions, such as atherosclerosis. However, although several studies have explored the NO₂-FA biological properties, the effects of these compounds on the angiogenic process remain unknown. Hence, the present study investigated the effects of the NO₂-FA (derivates from the nitration of linoleic and oleic acids at physiological concentrations) on angiogenesis process. It is demonstrated that the NO2-FA could act as pro-angiogenic mediators. This effect was observed not only in human endothelial cells but also in ex vivo and in vivo models. Using endothelial cells, it is showed that NO₂-FA failed to affect cell proliferation or influence cellular viability, but significantly stimulated cell migration. It was also found that the NO₂-FA might modulate the ex vivo sprouting of new vessels as well as the in vivo angiogenic process, while inducing the expression of the vascular endothelial growth factor, the main mediator of angiogenesis. The data are consistent with the hypothesis that the observed effects mediated by NO-dependent mechanisms, since the presence of a ^.NO scavenger abrogated the induced effects, whereas equimolar concentrations of its precursors, showed no effect on angiogenesis under our experimental conditions. Finally, the pro-angiogenic effects of NO2-FA were mediated by the stabilization of the hypoxia inducible factor-l1á (HIF-1á) protein, because these compounds increased the protein amount and failed to show inductive effects...

Comparative histological study of atherosclerotic lesions and microvascular changes in amputated lower limbs of diabetic and non-diabetic patients / Estudo histológico comparativo das lesões ateroscleróticas e alterações microvasculares em membros inferiores amputados de pacientes diabéticos e não-diabéticos

OBJETIVE: To perform a comparative analysis of atherosclerotic lesions and capillaries changes in diabetic and nondiabetic patients. METHODS: Leg arteries and skin of 57 amputated lower limbs of diabetic (47.3 percent) and nondiabetic patients were histologically examined. The percentage of arterial stenosis of infrapopliteal arteries and the histological classification of atherosclerotic lesions were determined. Capillary thickening was classified into four categories. RESULTS: Diabetic group showed more than 75 percent stenosis in 57 percent (vs. 56 percent in nondiabetic) of the anterior tibial; 78 percent (vs. 68 percent) of the posterior tibial; 58 percent (vs. 50 percent) of the peroneal leg arteries. Diabetic and nondiabetic patients have predominance of type VI atherosclerotic lesions. The comparison of both groups showed no significant differences in atherosclerotic lesions. Diabetic patients had significantly more PAS positive capillary thickening (63 percent vs. 23 percent). CONCLUSIONS: There were no differences in histological characteristics of atherosclerosis between the two groups. Capillary thickening has been more observed in diabetics.

OBJETIVO: Comparar as lesões ateroscleróticas das extremidades de diabéticos e não-diabéticos, estudando a ocorrência de espessamento capilar. MÉTODOS: Examinou-se segmentos arteriais e da derme de 57 membros inferiores amputados de diabéticos (47,3 por cento) e não-diabéticos. Analisou-se a porcentagem de estenose das artérias infra-poplíteas e a classificação histológica da placa. A presença de espessamento capilar foi classificada em quatro categorias. RESULTADOS: Entre os diabéticos 57 por cento (versus 56 por cento dos não-diabéticos) apresentavam estenose maior que 75 por cento da artéria tibial anterior; 78 por cento (versus 68 por cento) da tibial posterior; 58 por cento (versus 50 por cento) da fibular. Houve predominância em ambos de lesões ateroscleróticas do tipo VI. Comparando os grupos, não houve diferença significante na porcentagem de obstrução arterial ou na classificação da placa aterosclerótica. Os diabéticos apresentaram significativamente mais espessamento capilar (63 por cento versus 23 por cento). CONCLUSÕES: Não houve diferença nas características das lesões ateroscleróticas em diabéticos e não-diabéticos. O espessamento capilar foi mais prevalente entre os diabéticos.

A practical protocol to measure common carotid artery intima-media thickness

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Manejo de las dislipidemias en niños y adolescentes: [revisión] / Management of dyslipidemias in children and adolescents: [review]

Evidencia reciente confirma que la enfermedad cardiovascular se inicia en la infancia, y la dislipidemia es uno de los principales factores de riesgo asociados. La detección precoz de la hipercolesterolemia en niños con factores de riesgo, previene la morbimortalidad cardiovascular en el adulto. Se propone un esquema de detección y manejo de la dislipidemia, basado en la experiencia de grupos de expertos, así como medidas dietéticas y terapéuticas a seguir. Se debe hacer hincapié en cambios de estilo de vida a largo plazo, recomendando hábitos alimentarios saludables y ejercicio ya que la obesidad es la causa mas frecuente de dislipidemia en el niño. Existen varias alternativas farmacológicas, y en su uso y selección se debe evaluar el riesgo en forma individual, tomando en cuenta la edad, los niveles séricos de lípidos, la magnitud y el número de eventos cardiovasculares en familiares y los posibles efectos secundarios. Actualmente las estatinas están tomando un papel importante en el tratamiento de la hipercolesterolemia familiar en niños sin embargo se requieren más estudios a fin de establecer su seguridad en este grupo de edad. En vista que la hipercolesterolemia es un factor de riesgo modificable y determinante en la enfermedad cardiovascular, todas las intervenciones que se puedan hacer en la niñez, ofrecen una oportunidad de prevención.

Recent evidence corroborate that cardiovascular disease begins in childhood and that hyperlipidemia is one of the main associated risk factors. Early screening of hypercholesterolemia in high risk children should be performed in order to prevent cardiovascular morbidity and mortality in adulthood. An approach for detection and management of hypercholesterolemia is proposed with dietary and therapeutic strategies based on the experience of expert groups. Since obesity is the most common cause of hyperlipidemia in children, special emphasis should be made in long lasting lifestyle changes. Treatment always must include dietary modifications and exercise. Several pharmacologic alternatives are available, and when deciding its use, the child's risk must be individually analyzed, considering age, type and degree of dyslipidemia, and possible adverse effects. Since hypercholesterolemia is a modifiable and determinant risk in cardiovascular disease, all interventions done in childhood offer the opportunity of cardiovascular disease prevention in adulthood.

Carotid intima media thickness: an independent marker for assessment of macrovascular risk in diabetic patients.

In view of the global epidemic of diabetes with India being the hottest reservoir of the disease, it was tried to identify carotid intima media thickness as a surrogate marker for atherosclerosis in diabetic subjects. The study becomes more relevant because diabetes is now considered a disease of the endothelium and a risk equivalent of coronary atherosclerosis (paradigm shift). The study incorporated 41 normotensive patients of diabetes and 31 age and sex matched controls. Plasma glucose and lipid profiles were assessed in all and the carotid intima media thickness was measured. Results were statistically analysed for significance and correlation coefficient between values of plasma glucose and carotid intima media thickness. Results clearly showed that carotid intima media thickness abnormality can pick up atherosclerosis even if the lipid parameters are nearly normal. So it crystallises from this small study that, as a non-invasive test carotid intima media thickness is a better and early predictor of atherosclerosis in diabetic subjects. It also revealed the linear relationship between both fasting and postprandial blood sugar with carotid intima media thickness.

Densidad vascular disminuida en la pared de la aorta: Característica morfológica y funcional de la aterosclerosis / Diminished vascular density in the aortic wall: Morphological and functional characteristics of atherosclerosis

Antecedente: Por distribución irregular de aterosclerosis en paredes arteriales se buscó desproporción entre grosor de la pared vascular y vasa vasorum en ocho fragmentos de aorta humana. Método: Se midió longitud y grosor de pared y de sus capas y se contó vasa vasorum, se calculó densidad vascular como número de vasos por milímetro cuadrado en áreas sanas y enfermas, valor medio, varianza, desviación estándar e intervalo de confianza para valores y para hipótesis nula, se analizaron varianzas y se aplicó prueba "t" comparativa y pareada. Resultado: Hay diferencias de grosor entre íntima sana (27 micras) y enferma (120.5 micras), P < 0.001; y entre media sana (125.2 micras) y enferma (102.3 micras), P < 0.001. La densidad vascular es mayor en fragmentos sanos (media ± IC 99% = 4.4 ± 1.4 vs 2.2 ± 0.8, P < 0.001 para Ha; 0 ± 1.0775 para Ho; "t" pareada 2.1 ± 1.1, P < 0.01). Mayor ante íntima sana (31.6 vs 5.1, P < 0.01). No varía ante capa media. La relación entre número de vasos y longitud del segmento vascular es mayor en el fragmento sano (media ± IC 95% = 4.9 ± 1.02 vs 3.5 ± 0.68, diferencia 1.4, P < 0.05). Conclusión: La densidad vascular es menor en la pared de aorta aterosclerosa que en aorta sana lo que pudiera iniciar el proceso patógeno.

Purpose: To determine disproportion in thicknesses of the vascular wall and vasa vasorum in eight fragments of human aorta because of the irregular distribution of atherosclerosis in arterial walls. Method: The length and thickness of the wall and its layers were measured and the vasa vasorum were conted. Vascular density, considered as the number of vessels per square millimeter in healthy and diseased areas, was calculated along with mean value, variance, standard deviation and the confidence interval for values and null hypotesis. Variances were analyzed, and the comparative and paired "t" test was applied. Results: There were differences in thicknesses of the healthy (27 :m) and diseased (120.5 :m) intima (p < 0.001) and between the healthy (125.2 :m) and diseased (102.3 :m) media (P < 0.001). Vascular density was higher in healthy fragments (mean ± CI 99% = 4.40 ± 1.4 vs 2.20 ± 0.8, = < 0.001 for Ha; 0 ± 1.0775 for Ho; paired "t" 2.1 ± 1.1, P < 0.01), and higher compared to the healthy intima area (31.6 vs 5.1, P < 0.01). There were no differences compared to the media layer area. The relation between the number of vessels and the length of the vascular segments was greater in the healthy fragments (mean ± CI 95% = 4.9 ± 1.02 vs 3.5 ± 0.68; 1.4 difference, P < 0.05). Conclusion: Vascular density is lower in the atherosclerotic aortic wall than in the healthy aorta and this could initiate the pathologic process.

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease.

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.

Proteoglycans production by aortic vascular smooth muscle cells from hypertensive rats

Remodeling of large and small arteries contributes to the development and complications of hypertension. Artery structural changes in chronic sustained hypertension include vascular smooth muscle cells (VSMC) proliferation and extracellular matrix (ECM) modifications. Extracellular constituents such as proteoglycans (PGs), may modulate vascular stiffness and VSMC growth and differentiation. We examined the effect of growth factors on secreted and membrane-bound PGs synthesis by cultured aortic smooth muscle cells (SMC) from 12- to 14- week-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats. After stimulation with platelet-derived growth factor (PDGF-BB), 10% fetal calf serum (FCS) or 0.1% FCS as control, PGs synthesis (dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic label method using both [3H]-glucosamine and [35S]-sodium sulfate which are incorporated into all complex carbohydrates or only into sulfated dysaccharides, respectively. Data are presented as percent of the control (0.1% FCS). SHR VSMC displayed a significantly greater synthesis of M-ECM [3H]-PGs than Wistar rat cells, with both treatments, but no differences in M-ECM [35S] uptake were found in any case. In the P-ECM, both PDGF-BB and 10% FCS produced a greater effect on [3H]-PGs and sulfated PGs synthesis in VSMC from SHR. An important change seen in SHR cells was a significant decreased sulfation, assessed by [35S]/[3H] ratio, in basal and stimulation conditions. Present results indicate the existence of changes in PGS synthesis and modulation in VSMC from a conduit-artery of SHR and support the pathophysiological role proposed for matrix proteoglycans in the vascular wall changes associated to hypertension and related vascular diseases as atherosclerosis.

Chlamydia pneumoniae, Mycoplasma pneumoniae, fatores de crescimento e células inflamatórias nas lesões ateroscleróticas iniciais da aorta ascendente, em portadores de doença arterial coronária / Chlamydia pneumoniae, Mycoplasma pneumoniae, growth factors and inflammatory cells in the early atherosclerotic lesions of ascending aorta in patients with coronary artery disease

Chlamydia pneumoniae (CP), Mycoplasma pneumoniae (MP), linfócitos, macrófagos e fatores de crescimento (FC) foram pesquisados na íntima de lesões iniciais ateroscleróticas da aorta ascendente de 30 pacientes submetidos a cirurgia de coronária. Analisou a correlação entre: quantidade de macrófagos, CP e MP, linfócitos e o espessamento intimal (EI). CP esteve presente e em correlação com número de linfócitos T (CD4, CD8) e B (CD20), macrófagos (CD68) e MP se correlacionou quantidade de CP. Não houve correlação entre os FC e EI ou com o número de macrófagos CD68. Em conclusão, o estudo fala a favor de que CP está relacionada ao desenvolvimento da aterosclerose e da inflamação na íntima / Presence of Chlamydia pneumoniae(CP), Mycoplasma pneumoniae(MP), lymphocytes, macrophages and growth factors(GF) from the intima fragments of acending aorta from 30 patients submited to CABG. Analized correlation between: macrophages, CP and MP, lymphocytes and the intimal thickness (IT). The study showed that CP and MP are present in initial atherosclerotic lesions; Strong correlation of T (CD4, CD8) and B (CD20), macrophages (CD68) and MP with the mean numbers of CP positive cells suggest that CP is related with the development of atherosclerosis and with its inflamation. There was no correlation between growth factors and intimal thickness or with the mean number of CD68 macrophages...

experimental model for studying atherosclerosis

The aim of the present study was to clarify if old N-MRI rat, a strain which is easily available in Iran and cheap to maintain, is a suitable alternative to those previously reported. In this model, we compared three quantifiable parameters between old and young rats: biochemically, involving measurement of differences in the lipid profile. Histologically, the differences of the thickness of the wall of the aorta, the apparent degree of splitting within the aortic media, and the formation of foamy lipid layers on the outermost layer of the aorta. Pharmacologically, in vitro contractile responses/mg wet tissue weight to submaximal concentration of phenylephrine [1 micro M] and the rate of relaxation min-1 mg-1 tissue weight following administration of 0.1 mM of acetycholine. The proposed model was validated using lovastatin as test drug known for its lipid lowering and anti-atherosclerosis actions. The results showed that this model to be reliable, quantifiable and capable of detecting the effect of orally administered lovastatin. We recommend this model as an easy and accessible experimental model for various atheroscleorosis investigations