C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling

Pontus Boström, Nina Mann, Jun Wu, Pablo A. Quintero, Eva R. Plovie, Daniela Panáková, Rana K. Gupta, Chunyang Xiao, Calum A. MacRae, Anthony Rosenzweig, Bruce M. Spiegelman

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPβ was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPβ in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPβ levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPβ represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPβ is a central signal in physiologic hypertrophy and proliferation. PaperClip:

Original languageEnglish (US)
Pages (from-to)1072-1083
Number of pages12
JournalCell
Volume143
Issue number7
DOIs
StatePublished - Dec 23 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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