Abstract
Hypertrophy represents the major physiological response of the heart
to adapt to chronically enhanced workload, but is also crucial in
the development of heart failure. Although we know of numerous inducers
of cardiac hypertrophy, little is known about mechanisms that limit
cardiac hypertrophy. Here, we describe the transcriptional repressor
NAB1 as an endogenous regulator of cardiac growth. We identified
NAB1 as being upregulated in both mouse and human heart failure.
Nab1 is highly expressed in mammalian cardiac myocytes and it inhibited
cardiomyocyte hypertrophy through repression of its targets, transcription
factor Egr. Transgenic mice with cardiac-specific overexpression
of Nab1 showed that Nab1 is a potent inhibitor of cardiac growth
in response to pathological stimuli in vivo. Nab1 overexpression
suppressed adrenergically induced and pressure overload-induced hypertrophy,
whereas physiological growth during development and in response to
exercise was not affected. These findings implicate the Nab1-Egr1
axis as a crucial regulator of pathological cardiac growth.
Users
Please
log in to take part in the discussion (add own reviews or comments).