Thyroid Hormone and Cardiac Disease: From Basic Concepts to Clinical Application

Figure 2

Cardiac cells are de-differentiated upon exposure to progrowth stimuli such as phenylephrine (PE). This response is mediated via ERK/TRα1 and requires an intact mTOR signaling. Inhibition of mTOR signaling with rapamycin not only abolishes PE-induced nuclear TRα1 overexpression but results in marked TRα1 decrease with cell atrophy. De-differentiated cells retain the ability to re-differentiate when T3 is added to the medium. TRα1 by its dual action (liganded versus unliganded) seems to act as a regulator of the cell dedifferentiation/redifferentiation process.