Requirement of protein kinase D1 for pathological cardiac remodeling

Jens Fielitz, Mi Sung Kim, John M. Shelton, Xiaoxia Qi, Joseph A Hill, James A Richardson, Rhonda S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticlepeer-review

185 Scopus citations


The adult heart responds to biomechanical stress and neurohormonal signaling by hypertrophic growth, accompanied by fibrosis, diminished pump function, and activation of a fetal gene program. Class II histone deacetylases (HDACs) suppress stress-dependent remodeling of the heart via their association with the MEF2 transcription factor, an activator of heart disease. Protein kinase D (PKD) is a stress-responsive kinase that phosphorylates class II HDACs, resulting in their dissociation from MEF2 with consequent activation of MEF2 target genes. To test whether PKD1 is required for pathological cardiac remodeling in vivo, we generated mice with a conditional PKD1-null allele. Mice with cardiac-specific deletion of PKD1 were viable and showed diminished hypertrophy, fibrosis, and fetal gene activation as well as improved cardiac function in response to pressure overload or chronic adrenergic and angiotensin II signaling. We conclude that PKD1 functions as a key transducer of stress stimuli involved in pathological cardiac remodeling in vivo.

Original languageEnglish (US)
Pages (from-to)3059-3063
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 26 2008


  • Cardiac hypertrophy
  • Histone deacetylase
  • Stress-responsive kinase

ASJC Scopus subject areas

  • General


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