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Inducible and myocyte-specific inhibition of PKC enhances cardiac contractility and protects against infarction-induced heart failure

¹Department of Pediatrics, Cincinnati Children's Hospital Medical Center, and ²Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio

Submitted 23 April 2007 ; accepted in final form 1 October 2007

Mice null for the gene encoding protein kinase C (Prkca), or mice treated with pharmacologic inhibitors of the PKC/β/ isoforms, show an augmentation in cardiac contractility that appears to be cardioprotective. However, it remains uncertain if PKC itself functions in a myocyte autonomous manner to affect cardioprotection in vivo. Here we generated cardiac myocyte-specific transgenic mice using a tetracycline-inducible system to permit controlled expression of dominant negative PKC in the heart. Consistent with the proposed function of PKC, induction of dominant negative PKC expression in the adult heart enhanced baseline cardiac contractility. This increase in cardiac contractility was associated with a partial protection from long-term decompensation and secondary dilated cardiomyopathy after myocardial infarction injury. Similarly, Prkca null mice were also partially protected from infarction-induced heart failure, although the area of infarction injury was identical to controls. Thus, myocyte autonomous inhibition of PKC protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility.

protein kinase C; signaling; myocardial infarction

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