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 T-4 supplementation on left ventricle (LV) remodeling in 5/6 nephrectomized rats (5/6Nx) was analyzed. Methods. 5/6Nx rats and 5/6Nx under T-4 supplementation (5/6Nx + T-4) were compared with control (C) and thyroidectomized (Tx) rats. After 8 weeks of follow-up, LV was analyzed for alpha-MHC, beta-MHC, TGF-beta, 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 T-4 supplementation (C, 1.5 +/- 0.04; 5/6Nx, 1.8 +/- 0.09; 5/6Nx + T-4, 1.6 +/- 0.07 g, p < 0.05). The same pattern was seen for LV wall thickness, hydroxyproline content, LV fibrosis, and mRNA TGF-beta expression (C, 0.47 +/- 0.17; 5/6Nx, 10.55 +/- 3.4; 5/6Nx + T-4, 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 alpha-, beta-MHC, and TGF-beta increased in 5/6Nx in comparison to C and 5/6Nx + T-4. Expression of mir-208 decreased in 5/6Nx groups, and levels were restored with T-4 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-beta expression in the heart. (C) 2013 IMSS. Published by Elsevier Inc.