EXPRESSION OF PROTEIN-KINASE-C-BETA IN THE HEART CAUSES HYPERTROPHY IN ADULT MICE AND SUDDEN-DEATH IN NEONATES

Protein kinase C (PKC) activation in the heart has been linked to a hy pertrophic phenotype and to processes that influence contractile funct ion. To establish whether PKC activation is sufficient to induce an ab normal phenotype, PKC beta was conditionally expressed in cardiomyocyt es of transgenic mice. Transgene expression in adults caused mild and progressive ventricular hypertrophy associated with impaired diastolic relaxation, whereas expression in newborns caused sudden death associ ated with marked abnormalities in the regulation of intracellular calc ium. Thus, the PKC signaling pathway in cardiocytes has different effe cts depending on the timing of expression and, in the adult, is suffic ient to induce pathologic hypertrophy.