C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling

The heart has the ability to growin 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/EBP beta was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBP beta 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/EBP beta levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBP beta represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBP beta is a central signal in physiologic hypertrophy and proliferation.