PICOT: a multidomain scaffolding inhibitor of hypertrophic signal transduction.

Unlike the explosive hyperplastic growth that occurs during early embryonic development, neonatal and adult cardiomyocytes undergo hypertrophy as a consequence of a much more subtle increase in the fractional growth rate of the heart. Both physiological and pathological hypertrophy results from mechanical and neurohormonal signals (and their downstream effectors) that tend to increase the rate of cardiac protein synthesis. These growth-promoting pathways are counterbalanced by signaling molecules that tend to inhibit or attenuate the prohypertrophic growth response.1 In this issue of Circulation Research, Jeong et al2 continue to add to a growing list of negative regulators of cardiomyocyte hypertrophy, and describe how PICOT (protein kinase C–interacting cousin of thioredoxin) may function to inhibit the calcineurin (CnA)– nuclear factor of activated T cells (NFAT) signaling pathway responsible for regulating specific aspects of the hypertrophic phenotype.