Rapamycin prevents thyroid hormone-induced cardiac hypertrophy

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Biology

Background:

• Thyroid hormones (THs) are known to affect the cardiovascular system, including inducing cardiac hypertrophy.
• The precise molecular mechanisms underlying TH-induced cardiac hypertrophy remain largely unknown.
• Previous studies indicated THs activate protein synthesis signaling pathways like mammalian target of rapamycin (mTOR) and p70 S6 kinase in the heart.

Purpose of the Study:

• To investigate whether the AKT/mTOR/S6 kinase signaling pathway is essential for TH-induced cardiac hypertrophy.
• To determine if inhibiting mTOR function can prevent cardiac hypertrophy caused by thyroid hormones.

Main Methods:

• Mice (C57) and neonatal cardiomyocyte cultures were treated with thyroxine (T4) and/or rapamycin (an mTOR inhibitor) via slow-release pellets or direct administration.
• Hemodynamic and physical data were collected, and heart tissues were analyzed using Western blot.
• Primary neonatal cardiomyocytes were isolated and treated with triiodothyronine (T3) and rapamycin to assess signaling pathway activation.

Main Results:

• Thyroid hormones activated specific components of the AKT signaling pathway both in vivo and in vitro.
• THs induced cardiac hypertrophy, which was completely abrogated by rapamycin treatment.
• Rapamycin effectively inhibited the mTOR/S6 kinase signaling pathway.

Conclusions:

• The AKT/mTOR/S6 kinase signaling pathway plays a critical role in mediating thyroid hormone-induced cardiac hypertrophy.
• Inhibition of this pathway effectively prevents cardiac hypertrophy caused by thyroid hormones.
• These findings highlight a novel therapeutic target for managing conditions involving excessive cardiac growth due to thyroid hormone excess.