No cardiac hypertrophy induced by T3 in a mouse model of the syndrome of resistance to thyroid hormones

Abstract

Triiodotironine (T3) is critical for cardiac function. Heart expresses TRα1 e TRβ1, the two main thyroid hormone (TH) receptors (TR). We aimed to investigate the role of TRβ1 on T3‐induced cardiac hypertrophy.Adult male mice, wild‐type (WT) or homozygous (HO) for Δ337T mutation on TRβ (unable to bind T3), were used. Animals were studied at baseline, after hypo‐ (PTU) and hyperthyroidism (PTU+T3) induction. Echo‐ and electrocardiogram were performed. Hearts were collected, weighed and total RNA was extracted. Expression of mRNA and miRNAs were quantified by real time RT‐PCR.T3 caused cardiac hypertrophy in WT, but not in HO animals when evaluated by cardiac index (P<0.001) or by echocardiography (25%, P<0.05). Genes responsive to T3 as ARb1, SERCa2 and HCN2 were responsive to T3 in WT but not in HO. Absence of a functional TRβ1 altered several parameters in HO cardiac function. Stroke volume and ejection fraction dropped in HO‐PTU+T3 vs. HO‐PTU. P wave reduced (50%, P<0.001) and heart rate increased (P<0.05) on WT‐PTU+T3 vs. WT‐PTU; but not in HO. Analysis of MicroRNAs miR‐1 and miR‐208, involved in cardiac hypertrophy, showed that T3 treatment increased both (2 to 3 times) in a different fashion, being miR‐1 TRβ independent and miR‐208 TRβ dependent.TH‐induced cardiac hypertrophy is TRβ‐dependent and involves miR‐208, while the absence of T3 ligation on TRβ promotes a significant deterioration in cardiac function.