Calcineurin/NFAT Coupling Participates in Pathological, but Not Physiological, Cardiac Hypertrophy

Nine years ago, we published an article that suggested a specialized role for calcineurin–nuclear factor of activated T-cells (NFAT) signaling in regulating pathologi-cal cardiac hypertrophy preferentially over physiological growth and, in fact, the later response was associated with reduced calcineurin–NFAT activity. Since this time we and others have continued to uncover how this signaling effec-tor pathway functions in the heart in regulating specific aspects of the growth response during disease and with exercise. Pathological cardiac hypertrophy is associated with neuro-endocrine dysregulation after myocardial infarction injury or in response to long-standing hypertension, as well as in re-sponse to a myriad of other disease-causing stimuli, whereas physiological hypertrophy of the heart occurs with intense exercise training.1,2 Although the heart enlarges under bot