Role of thyroid hormones and mir-208 in myocardial remodeling in 5/6 nephrectomized rats.
OBJECTIVE
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.
Medical Research Unit in Nephrology Diseases, Specialty Hospital, Centro Médico Nacional Siglo XXI, Mexican Social Security Institute, Mexico City, Mexico. Electronic address: carpradou@gmail.com.
María-Del-Carmen
MD
Prado-Uribe
María-Virgilia
MV
Soto-Abraham
Carmen J
CJ
Mora-Villalpando
Juan M
JM
Gallardo
Edmundo
E
Bonilla
Marcela
M
Avila
Eduardo
E
Tena
Ramón
R
Paniagua
D000818:Animals; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000737:chemistry / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
C569395:MIRN208 microRNA, rat; D035683:MicroRNAs; D013963:Thyroid Hormones; D016212:Transforming Growth Factor beta
Chronic kidney disease; Heart failure; Heart fibrosis; Myocardial remodeling; Thyroid hormone; mir-208