Early intervention with simvastatin exerts improved effects on cardiac hypertrophy in pressure-overload rats than late intervention

AIM: To compare the effects of early and late intervention with simvastatin on cardiac hypertrophy and to investigate the probable molecular mechanisms. METHODS: In pressure-overload rat model induced by abdominal aortic coarctation, simvastatin ［10 mg/(kg·day), IG］ was administrated at early or late stage and structural and functional changes were observed by histopathology analysis with picrosirius staining and hemodynamic measurement. The expression of TNF-α and IL-6 and IL-10 protein levels were determined by ELISA and the production of reactive oxygen species (ROS). Activity of NAPDH oxidase in myocardium were measured, respectively, by Fenton reaction and by superoxide dismutase inhibitable cytochrome C reduction assay. RESULTS: In rats at 8 weeks after aortic coarctation, the left ventricle weight and collagen volume fraction in myocardium significantly increased and cardiac diastolic function decreased, compared with those in sham-operated rats (P<0.01). Intervention with simvastatin at early and late stages both markedly decreased the left ventricle weight and collagen volume fraction (P<0.05). However, left ventricle weight and collagen volume fraction in early intervention group were lower than those in late intervention group (P<0.05). The early intervention also improved the diastolic function and the contents of TNF-α and IL-6. ROS production and NADPH oxidase activity in myocardium were all elevated in pressure-overload rats, which were attenuated by simvastatin intervention at both stages. Contents of TNF-α and IL-6, production of ROS, and activity of NADPH oxidase in rats in early intervention group were lower than those in late intervention group (P<0.05). CONCLUSION: The effects of early intervention with simvastatin on cardiac hypertrophy in pressure-overload rats are superior to those of late intervention, which is probably attributed to the stronger inhibitory effects of early intervention with simvastatin on the expression of proinflammatory cytokines and production of ROS.