Excessive Reactive Oxygen Species (ROS) production is involved in cardiac pathologies such as hypertrophy. Protein tyrosine phosphatases are regulated by reversible oxidation via ROS production. We demonstrated that in murine hearts undergoing hypertrophy, ROS production was associated with inactivation of the protein tyrosine phosphatase PTP1B. Moreover, PTP1B cardiac knockout (cKO) mice showed an exacerbated cardiac hypertrophy when subjected to pressure overload by transverse aortic constriction (TAC). Preventing thyroid hormone synthesis reversed the PTP1B-inactivation-driven pathological remodeling.

Our aim was to investigate the protein expression of thyroid hormone-responsive genes possibly involved in the hypertrophic phenotype of TAC PTP1B cKO mice and in the bradycardia observed in cKO mice.

4 weeks post-surgery, TAC and sham hearts were harvested from control or PTP1B cKO mice for immunobloting from protein lysates. The protein expression of β-Myosin Heavy Chain (MHC), thyroid receptor alpha1 and beta 1 (TRα1, TRβ1), hyperpolarization-activated cyclic nucleotide-gated channels2/4 (HCN2, HCN4) and sarcoplasmic reticulum calcium ATPase2 (SERCA2) were studied.

TAC hearts from PTP1B cKO mice showed a decreased expression of β-MHC and an increased expression of TRα1. TRβ1 was upregulated in both control and hypertrophic PTP1B cKO mice but SERCA2 or HCN4 protein levels did not show any significant differences between the two groups, subjected to TAC or not.

Thyroid hormone signaling is altered following PTP1B inactivation in the heart and appears to occur mainly through changes in TRs isoforms expression. The limited sample size from our study (n=2) did not allow us to conclude definitely about HCN4 and SERCA2 expressions. Additional experiments will need to be performed to gain further insight on molecular mechanisms whereby PTP1B inactivation affects cardiac function and thyroid hormone signaling.