Thyroid‐stimulating hormone regulates cardiac function through modulating HCN2 via targeting microRNA ‐1a

Abstract

Previous studies have found microRNA‐1 (miR‐1) and hyperpolarization‐activated cyclic nucleotide‐gated channel 2 (HCN2) may be involved in the pathogenesis of thyroid hormone (TH) induced cardiac hypertrophy. However, little is known about the role of miR‐1 and HCN2 in thyroid stimulation hormone (TSH)‐induced cardiac dysfunction. In order to investigate the molecular mechanisms of TSH induced cardiac dysfunction and the role of miR‐1/HCN2 in that process, we evaluated the expression of miR‐1a/HCN2 in the ventricular myocardium of hypothyroid mice and in TSH‐stimulated H9c2 cardiomyocytes. Our data revealed that hypothyroidism mice had smaller hearts, ventricular muscle atrophy, and cardiac contractile dysfunction compared with euthyroid controls. The upregulation of miR‐1a and downregulation of HCN2 were found in ventricular myocardium of hypothyroid mice and TSH‐stimulated H9c2 cardiomyocytes, indicating that miR‐1a and HCN2 may be involved in TSH‐induced cardiac dysfunction. We also found that the regulation of miR‐1a and HCN2 expression and HCN2 channel activity by TSH requires TSHR, while the regulation of HCN2 expression and HCN2 channel function by TSH requires miR‐1a. Thus, our data revealed the potential mechanism of TSH‐induced cardiac dysfunction and might shed new light on the pathological role of miR‐1a/HCN2 in hypothyroid heart disease.

Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States

“…To our knowledge, no reports have been shown on these targets and warrant further investigation. Numerous studies have shown the vital roles of miRNAs in cardiovascular disorders [ 16 , 17 , 18 , 48 , 49 , 50 , 51 ]. In this study, we have also uncovered hundreds of significantly altered and novel miRNAs in TH-mediated cardiac regulation ( Supplementary File S7 ).…”

“…Studies have also shown functional involvement of miRNAs in the heart associated with thyroid dysfunction [ 48 , 49 , 50 , 51 ]. A recent study from our group highlighted that the T3-induced protection from cardiac decompensation secondary to acute severe caloric restriction is partly mediated by lncRNAs [ 52 ].…”