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

Area of Science:

• Cardiology
• Molecular Biology
• Endocrinology

Background:

• Thyroid hormone (TH) impacts cardiac function.
• MicroRNA-1 (miR-1) and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) are implicated in TH-induced cardiac hypertrophy.
• The role of miR-1 and HCN2 in thyroid stimulation hormone (TSH)-induced cardiac dysfunction remains unclear.

Purpose of the Study:

• To investigate the molecular mechanisms of TSH-induced cardiac dysfunction.
• To elucidate the role of miR-1 and HCN2 in TSH-induced cardiac dysfunction.

Main Methods:

• Evaluated miR-1a and HCN2 expression in hypothyroid mouse hearts and TSH-stimulated H9c2 cardiomyocytes.
• Assessed cardiac structure and function in hypothyroid mice.
• Investigated the involvement of TSH receptor (TSHR) and miR-1a in TSH's regulation of HCN2.

Main Results:

• Hypothyroidism led to smaller hearts, ventricular atrophy, and contractile dysfunction.
• miR-1a was upregulated, and HCN2 was downregulated in hypothyroid hearts and TSH-stimulated cardiomyocytes.
• TSH regulation of miR-1a and HCN2 expression/activity requires TSHR and miR-1a.

Conclusions:

• miR-1a and HCN2 are potentially involved in TSH-induced cardiac dysfunction.
• This study reveals a molecular mechanism for TSH-induced cardiac dysfunction.
• Findings offer new insights into the role of miR-1a/HCN2 in hypothyroid heart disease.