Objective: To determine the mechanism by which muscle-specific microRNA (miR-206) and the miR-206 target gene insulin-like growth factor (IGF-1) cause myocardial damage in hypothyroidism rat models.
Methods: Wistar rats were grouped into normal (C) and Hypothyroidism (H) groups. Sixteen weeks after successful modeling, eight rats were picked randomly from the hypothyroidism group for levothyroxine (L-T4) treatment (HL). The patterns of myocardial tissue pathology were elucidated; the expressions of α-Myosin Heavy Chain (MHC), β-MHC, miR-206, and IGF-1 in the myocardial tissue were also measured.
Results: Rat myocardial α-MHC and IGF-1 protein expression in group H rats displayed a clear decrease (0.325 ± 0.027 and 0.101 ± 0.004, respectively, in H vs. 1.008 ± 0.137 and 0.149 ± 0.003 in C; P<0.01). In contrast, myocardial β-MHC expression showed a 2.539-fold increase in group H compared to group C (3.695 ± 1.516, P<0.05). Rat myocardial α-MHC expression was significantly increased in group HL compared to group H (1.078 ± 0.274 vs. 0.325 ± 0.027, P<0.01). However, β-MHC expression showed a clear decrease. The expression of miR-206 was also significantly decreased (1.488 ± 0.946, P<0.05) and that of IGF-1 protein increased compared to that seen in group H (0.160 ± 0.001 vs. 0.101 ± 0.004, P<0.01).
Conclusion: Myocardial miR-206 in hypothyroidism rat models inhibited IGF-1 transcription, which could be a partial cause of hypothyroidism-mediated cardiac disease. These changes in the hypothyroidism rat myocardium could be corrected using L-T4.