Cardiovascular Research Advance Access [Accepted Manuscript] published online on July 3, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp226
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Proteasome Inhibitors and Cardiac Cell Growth
Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, MSB G-609, Newark, NJ 07103- USA
* Corresponding author Tel: (973) 972-3926, Fax: (973) 972-7489, Email address: deprech{at}umdnj.edu
Activation of the ubiquitin-proteasome system has been described in different models of cardiac hypertrophy. Cardiac cell growth in response to pressure or volume overload, as well as physiological adaptive hypertrophy, is accompanied by an increase in protein ubiquitination, proteasome subunit expression and proteasome activity. Importantly, an inhibition of proteasome activity prevents and reverses cardiac hypertrophy and remodeling in vivo. The focus of this review is to provide an update about the mechanisms by which proteasome inhibitors affect cardiac cell growth in adaptive and maladaptive models of cardiac hypertrophy. In the first part, we summarize how the proteasome affects both proteolysis and protein synthesis in a context of cardiac cell growth. In the second part, we show how proteasome inhibition can prevent and reverse cardiac hypertrophy and remodeling in response to different conditions of overload.
Time for primary review: 34 Days