Role of thyroid hormones and mir-208 in myocardial remodeling in 5/6 nephrectomized rats.

Background And Aims: Thyroid hormones exert important effects on heart remodeling through mir-208. The process may have a role in myocardial changes in chronic kidney disease where thyroid abnormalities are common. In this study the effect of T4 supplementation on left ventricle (LV) remodeling in 5/6 nephrectomized rats (5/6Nx) was analyzed.

Methods: 5/6Nx rats and 5/6Nx under T4 supplementation (5/6Nx + T4) were compared with control (C) and thyroidectomized (Tx) rats. After 8 weeks of follow-up, LV was analyzed for α-MHC, β-MHC, TGF-β, and mir-208 expression, hydroxyproline content, and myocardial fibrosis. Serum collagenase activity was also analyzed.

Results: Heart weight increased in 5/6Nx rats compared to C, which was prevented with T4 supplementation (C, 1.5 ± 0.04; 5/6Nx, 1.8 ± 0.09; 5/6Nx + T4, 1.6 ± 0.07 g, p <0.05). The same pattern was seen for LV wall thickness, hydroxyproline content, LV fibrosis, and mRNA TGF-β expression (C, 0.47 ± 0.17; 5/6Nx, 10.55 ± 3.4; 5/6Nx + T4, 3.01 ± 0.52, p <0.01). Tx rats had reduction in heart weight, increased LV wall thickness, and fibrosis. Collagenase activity did not change in any group. mRNA expression of α-, β-MHC, and TGF-β increased in 5/6Nx in comparison to C and 5/6Nx + T4. Expression of mir-208 decreased in 5/6Nx groups, and levels were restored with T4 supplementation (4.21 ± 0.28, 3.39 ± 0.29, and 4.26 ± 0.37 RU, respectively, p <0.01).

Conclusions: Decreased plasma level of thyroid hormones or sensitivity at tissue level observed in chronic kidney disease induced by 5/6Nx has an important effect in heart remodeling processes, some of it related or mediated by mir-208 and TGF-β expression in the heart.