Abstract 318: Vitamin E Affects Pathological Cardiac Hypertrophy and MicroRNAs Expression in Mice

Abstract

Aims: Vitamin E is a usual antioxidant, but little is known about its effects on cardiac hypertrophy and microRNAs (miRs) expression induced by transverse aortic constriction (TAC) in mice. Methods and Results: Male Balb/c mice were randomly divided into four cohorts: SHAM ( n= 22), TAC ( n =34), SHAM supplemented with vitamin E (SHAM+VIT, n =22), and TAC supplemented with vitamin E (TAC+VIT, n =34). VIT groups received 200 mg/kg of α-tocopherol once a day, and the other groups received placebo, both by gavage. After 7 and 35 days of surgery analysis of cardiac hypertrophy, fibrosis, miRs and gene expression and carbonyl concentrations in cardiac tissue were performed. Left ventricle mass increased 23% and 35% in 7 and 35 days, respectively, in TAC group, similar data were observed in TAC+VIT group (all p <0.05 vs. SHAM groups). Cardiac fibrosis was increased by TAC surgery as early as 7 days and remained high after 35 days. Still, TAC mice exhibit higher levels of protein damage at 35 days. This pathological phenotype was not seen in animals of the TAC+VIT group. Vitamin E seemed to inhibit cardiac fibrosis and oxidative damage. Moreover, cardiac hypertrophy was followed by increased miR-21 and -499 expression in TAC group, mainly 35 days ( miR-21 : 2.9 ± 0.6 fold vs . SHAM: 1 ± 0.1 fold , miR 499 : 3 ± 0.4 fold vs. 1.1 ± 0.1 fold , p <0.05). However, TAC+VIT mice displayed a different miR expression profile, with decreased miR-21 and - 499 expression ( miR-21 : 0.5 ± 0.1 fold , miR-499 : 0.4 ± 0.1 fold ; TAC vs. p <0.05) and increased miR-210 expression (3.2 ± 0.5 fold vs. TAC: 1.9 ± 0.2 fold, p =0.034). Computational target prediction of these miRs demonstrated that they can be involved in the control of major pathways in the heart disease scenario such as MAPK, mTOR, PI3K-AKT, among others. Conclusion: TAC model induced pathological cardiac hypertrophy, fibrosis and protein damage followed by changes in miRs expression. Vitamin E supplementation was associated with a different miR expression profile and mitigated the pathological phenotype.