ABSTRACT
La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.
Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.
Subject(s)
Animals , Male , Rats , Aorta/drug effects , Aortic Diseases/prevention & control , Diabetes Mellitus, Experimental/drug therapy , Diabetic Angiopathies/prevention & control , Endothelium, Vascular/drug effects , Glycosaminoglycans/therapeutic use , Hypoglycemic Agents/therapeutic use , Vasodilation/drug effects , Acetylcholine/pharmacology , Aorta/pathology , Aorta/physiopathology , Aortic Diseases/etiology , Aortic Diseases/pathology , Aortic Diseases/physiopathology , Drug Evaluation, Preclinical , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Angiopathies/etiology , Diabetic Angiopathies/pathology , Diabetic Angiopathies/physiopathology , Endothelium, Vascular/ultrastructure , Glycosaminoglycans/metabolism , Glycosaminoglycans/pharmacology , Hypoglycemic Agents/pharmacology , Nitroprusside/pharmacology , Rats, Sprague-Dawley , Tunica Intima/drug effects , Tunica Intima/ultrastructureABSTRACT
Los sistemas de prevención cardiovascular basados en la determinación de factores de riesgo presentan limitaciones para cuantificar el riesgo de un sujeto. Los factores de riesgo son predictores de aterosclerosis en la población, pero fallan en identificar qué sujetos desarrollarán la enfermedad y/o tendrán eventos cardiovasculares; los que frecuentemente se presentan en sujetos de riesgo bajo o intermedio. En este contexto, guías/consensos sugieren realizar estudios no invasivos en sujetos asintomáticos para estratificar el riesgo individual, detectar y tratar la aterosclerosis en etapa subclínica. Para ello se han propuesto diferentes abordajes que permiten caracterizar la estructura y/o función arterial por métodos no invasivos, brindando información complementaria, que adiciona a la obtenida con la determinación de los factores de riesgo. En Uruguay, recientemente se creó un centro universitario interdisciplinario (CUiiDARTE, Centro Universitario de Investigación, Innovación y Diagnóstico Arterial), que tiene entre sus objetivos implementar técnicas no invasivas para la evaluación integral de la estructura y función arterial, posibilitando dar respuesta a la necesidad de estratificación individualizada del riesgo cardiovascular y detección de aterosclerosis subclínica. En este trabajo se presenta el abordaje de evaluación vascular empleado en CUiiDARTE y basados en nuestra experiencia, se discuten aspectos teóricos y prácticos de los test no invasivos utilizados y parámetros estudiados.
Traditional risk factors-guided cardiovascular prevention/treatment has clear limitations in individual subjects management. Often, individuals with similar risk factor profiles have differences in the atherosclerosis development and are at different cardiovascular risk. Therefore, while risk factors are good predictors of atherosclerosis in a population, they cannot identify who will develop the disease and/or will have a cardiovascular event. In this context, there have been published guidelines calling for non-invasive atherosclerosis screening and risk stratification in asymptomatic subjects. Several approaches have been proposed for the vascular evaluation, and although the screening tests used vary among laboratories, in general terms their are underused. In Uruguay, it was recently created an interdisciplinary university center (CUiiDARTE, Centro Universitario de Investigación, Innovación y Diagnóstico Arterial), which has as a main aim the implementation of non-invasive techniques to evaluate the arterial structural and functional properties, that could allow stratifying the individual cardiovascular risk and identifying sub-clinical atherosclerosis. In this work we present the integral vascular approach used in CUiiDARTE and based in our experience we discuss, theoretical and practical issues related with the tests performed and parameters calculated.
Subject(s)
Humans , Carotid Arteries/ultrastructure , Carotid Arteries , Atherosclerosis/diagnosis , Atherosclerosis , Carotid Artery Diseases/diagnosis , Carotid Artery Diseases/prevention & control , Ankle Brachial Index , Aorta/physiology , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/prevention & control , Risk Factors , Blood Pressure , Tunica Intima/ultrastructure , Ultrasonography, Doppler, PulsedABSTRACT
OBJECTIVE: To observe the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats. METHODS: Thirty female Sprague Dawley rats (200- 250 g) were divided equally into five groups. One group served as the normal control (NC) group. The four treated groups were ovariectomized and were fed as follows: 2 percent cholesterol diet (OVXC); 2 percent cholesterol diet + fresh soy oil (FSO); 2 percent cholesterol diet + once-heated soy oil (1HSO); and 2 percent cholesterol diet + five-times-heated soy oil (5HSO). After four months, the rats were sacrificed, and the aortic tissues were obtained for histological studies. RESULTS: After four months of feeding, the NC, FSO and 1HSO groups had a lower body weight gain compared to the OVXC and 5HSO groups. The tunica intima/media ratio in the 5HSO group was significantly thicker (p < 0.05) compared to the NC, OVXC and FSO groups. Electron microscopy showed that endothelial cells were normally shaped in the FSO and NC groups but irregular in the 1HSO and 5HSO groups. A greater number of collagen fibers and vacuoles were observed in the 5HSO group compared to the other treatment groups. CONCLUSIONS: Fresh soy oil offered protection in the estrogen-deficient state, as these rats had similar features to those of the NC group. The damage to the tunica intima and the increase in the ratio of tunica intima/media thickness showed the deleterious effect of consuming repeatedly heated soy oil in castrated female rats.
Subject(s)
Animals , Female , Rats , Aorta, Thoracic/drug effects , Atherosclerosis/prevention & control , Estrogens/deficiency , Soybean Oil/pharmacology , Aorta, Thoracic/ultrastructure , Atherosclerosis/pathology , Disease Models, Animal , Dietary Fats, Unsaturated/pharmacology , Hot Temperature , Ovariectomy , Random Allocation , Rats, Sprague-Dawley , Tunica Intima/ultrastructureABSTRACT
PURPOSE: This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations. METHODS: Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer. RESULTS: A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers). CONCLUSIONS: The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.
OBJETIVO: Avaliar a inclusão em glicol metacrilato para estudar alterações morfológicas de veias safenas humanas submetidas a pressurizações breves e crescentes. MÉTODOS: Veias safena de 20 pacientes submetidos a cirurgia de revascularização do miocárdio foram distribuídas ao acaso em quatro grupos experimentais (controle, pressões de 100, 200 e 300 mmHg durante 15 segundos). Para quantificar a percentagem da superfície venosa recoberta por endotélio utilizou-se o aumento de 100x. A análise morfométrica foi realizada utilizando-se videomicroscopia com auxílio do software Leica Qwin em conjunto com um microscópio Leica e videocâmera, acoplados a um computador. RESULTADOS: Observou-se uma leve tendência de aumento quantitativo de todos os parâmetros avaliados, incluindo a percentagem de superfície recoberta por endotélio e a espessura das paredes das veias safenas. CONCLUSÕES: A inclusão em glicol metracrilato permitiu secções com adequada resolução dos detalhes estruturais, revelando-se um método extremamente útil para o estudo de veias safenas humanas pressurizadas.