ABSTRACT
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.
Subject(s)
Animals , Male , Rabbits , Arteriosclerosis/prevention & control , Cyclic N-Oxides/administration & dosage , Thioctic Acid/administration & dosage , Vascular Calcification/prevention & control , Aorta, Thoracic , Arteriosclerosis/chemically induced , Arteriosclerosis/metabolism , Compliance/drug effects , Compliance/physiology , Disease Models, Animal , Spin Labels , Vascular Resistance , Vascular Calcification/chemically induced , Vasoconstriction/drug effects , Vasoconstriction/physiologySubject(s)
Female , Humans , Cardiovascular Diseases/prevention & control , Health Promotion , Aspirin/therapeutic use , Brazil , Evidence-Based Medicine , Hypertension/prevention & control , Meta-Analysis as Topic , Quality of Life , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
Background: Botanical omega-3 fatty acid (alphalinolenic acid/ALA) has been shown to alleviate the prothrombotic and proinflammatory profile of metabolic syndrome, however clinical protocols are still scarce. Aiming to focus an obese population, a pilot study was designed. Methods: Morbidly obese candidates for bariatric surgery (n = 29, age 46.3 ± 5.2 years), 82.8% females (24/29), BMI 44.9 ± 5.2 kg/m2, with C-reactive protein/CRP > 5 mg/L were recruited. Twenty were randomized and after exclusions, 16 were available for analysis. Flaxseed powder (60 g/day, 10 g ALA) and isocaloric roasted cassava powder (60 g/day, fat-free) were administered in a double-blind routine for 12 weeks. Results: During flaxseed consumption neutrophil count decreased and fibrinogen, complement C4, prothrombin time and carotid diameter remained stable, whereas placebo (cassava powder) was associated with further elevation of those measurements. Conclusions: Inflammatory and coagulatory markers tended to exhibit a better outlook in the flaxseed group. Also large-artery diameter stabilized whereas further increase was noticed in controls. These findings raise the hypothesis of a less deleterious cardiovascular course in seriously obese subjects receiving a flaxseed supplement (AU)
Introducción: Los ácidos grasos botánicos omega-3 (ácido alfa-linolénico/ALA) se muestran convenientes para atenuar las características protrombóticas y proinflamatórias del síndrome metabólico, pero protocolos clínicos todavía son escasos. Con el objetivo de enfocar una población obesa, un estudio clínico fue dibujado. Métodos: Candidatos a cirugía bariátrica morbidamente obesos (n = 29, edad 46,3 ± 5,2 años), 82,8% mujeres (24/29), IMC 44,9 ± 5,2 kg/m2, con proteína C reactiva/CRP > 5 mg/L fueron recrutados. Veinte fueron randomizados y após exclusiones, 16 se puderon analisar. Harina de linaza (60 g/día, 10 g ALA) y harina de casava tostada isocalórica (60 g/día, sin grasas) fueron suministradas em uma rutina doble-ciega por 12 semanas. Resultados: Mientras se recibió linaza los neutrófilos bajaron y fibrinógeno, complemento C4, tiempo de protrombina y diámetro de la carótida permanecieron estables. El uso de casava se asoció con elevación de todas estas variables. Conclusiones: Los marcadores inflamatórios y coagulatórios tuvieron un curso mas favorable con la linaza. Asimismo el diámetro arterial se quedó estable, en cambio hubo peor a en el segundo grupo. La hipótesis de una evolución cardiovascular menos deletérea en obesos graves recibiendo casava se plantea en estas circunstancias (AU)
