Type 3 iodothyronine deiodinase is expressed in human induced pluripotent stem cell derived cardiomyocytes.

AIMS: Type 3 iodothyronine deiodinase (D3), which converts thyroxine (T4 ) and 3,5,3'-triiodothyronine (T3 ) to 3,3',5'-triiodothyronine (rT3 ) and 3,3'-diiodothyronine (T2 ), respectively, inactivates thyroid hormones. We investigated the expression and regulation of D3 in human cardiomyocytes which were differentiated from human induced pluripotent stem cells (hiPSCs).

MAIN METHODS: We characterized D3 activity using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. D3, myosine heavy chain α and β (MHCα and β, respectively), sarcoplasmic reticulum calcium ATPase (SERCA), and phospholamban (PLB) mRNA levels were analyzed by quantitative real-time PCR (qPCR) in hiPSC-derived cardiomyocytes (hiPS-CMs).

KEY FINDINGS: We identified enzyme activity that catalyzes the conversion of T3 to T2 in both hiPS-CMs and hiPSCs, which showed characteristics compatible with those for D3. D3 mRNA was identified in these cells using qPCR analysis. T3 and hypoxia mimetics such as CoCl2 and DFO, increased the D3 mRNA level in both hiPS-CMs and hiPSCs. Addition of iopanoic acid, a competitive inhibitor of iodothyronine deiodination, in the culture medium of hiPS-CMs, increased the mRNA levels such as MHCα and β, SERCA, and PLB induced by T3 .

SIGNIFICANTS: Our findings indicate that D3 is expressed in hiPS-CMs, and may decrease the intracellular T3 concentration, and may decrease the expression of cardiac genes such as MHCα and β, SERCA, and PLB in hiPS-CMs.