A20 Is Dynamically Regulated in the Heart and Inhibits the Hypertrophic Response

S. A. Cook
2003 Circulation  
Background-Nuclear factor (NF)-B signaling has been implicated in cardiomyocyte hypertrophy. Here, we determine the cardiac regulation and biological activity of A20, an inhibitor of NF-B signaling. Methods and Results-Mice were subjected to aortic banding, and A20 expression was examined. A20 mRNA upregulation (4.3Ϯ1.5-fold; PϽ0.05) was detected 3 hours after banding, coinciding with peak NF-B activation. A20 was also upregulated in cultured neonatal cardiomyocytes stimulated with
more » ... or endothelin-1 (2.8Ϯ0.6-and 4Ϯ1.1-fold, respectively; PϽ0.05), again paralleling NF-B activation. Infection of cardiomyocytes with an adenoviral vector (Ad) encoding A20 inhibited tumor necrosis factor-␣-stimulated NF-B signaling with an efficacy comparable to dominant negative inhibitor of -B kinase ␤ (dnIKK␤). Ad.dnIKK␤-infected cardiomyocytes exhibited increased apoptosis when they were serum starved or subjected to hypoxia-reoxygenation, whereas Ad.A20-infected cardiomyocytes did not. Expression of Ad.A20 inhibited the hypertrophic response in cardiomyocytes stimulated with phenylephrine or endothelin-1. Conclusions-A20 is dynamically regulated during acute biomechanical stress in the heart and functions to attenuate cardiac hypertrophy through the inhibition of NF-B signaling without sensitizing cardiomyocytes to apoptotic cell death. (Circulation. 2003;108:664-667.)
doi:10.1161/01.cir.0000086978.95976.41 pmid:12900338 fatcat:uxiw2ylllvaavgesqzzyq6abmm