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Background Soy isoflavones may affect several biochemical pathways like the synthesis of nitric oxide (•NO) and heat shock proteins (HSP) that are important factors for atherosclerosis development. Aim of the study The purpose of this study was to investigate the influence of soy isoflavones on the production of •NO and HSP60, HSP70 and HSC70 in experimental atherosclerosis. Methods One group of rabbits (New Zealand) was fed an atherogenic diet containing 27 % casein (CAS) and another group was fed the same diet supplemented with soy isoflavones (5 mg/kg/day) (ISO). Blood samples were obtained monthly and after six months of feeding, the rabbits were sacrificed and the aortas were removed. Results The ISO group showed a significant reduction of cholesterol in LDL (36.2 %) and in aorta (36 %), as well as, an increase of HDL-cholesterol (2.1 times) in relation to the CAS group. The concentration of •NO metabolites (NOx) in blood plasma and the levels of reactive antibodies to HSC70 in blood plasma and to HSC70 and HSP70 in aortic tissue were significantly decreased in the ISO group. Isoflavones promoted a reduction of content of HSP60, HSP70 and HSC70 in aortic arch analyzed by immunohistochemistry. The isoflavone supplementation promoted a reduction of cholesterol content in aorta (62.2 %) (p<0.05). Conclusions Soy isoflavones reduced hypercholesterolemia, the production of HSP60, HSC70 and HSP70 and reactive antibodies to HSC70 in serum and to HSC70 and HSP70 in aorta, as well as, the cholesterol content in atherosclerotic lesions in rabbits fed a casein-based atherogenic diet. [ABSTRACT FROM AUTHOR]