Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure

• DOI: 10.1073/pnas.0602543103
• Publication Date: 2006-09-19T00:57:41Z
• Authors: Egbert Bisping; Sadakatsu Ikeda; Sek Won Kong; Oleg Tarnavski; Natalya Bodyak; Julie R. McMullen; Satish Rajagopal; Jennifer K. Son; Qing Ma; Zhangli Springer; Peter M. Kang; Seigo Izumo; William T. Pu
• Keywords: Pressure overload; GATA4; Cardiac Fibrosis; Cardiac myocyte

An important event in the pathogenesis of heart failure is development pathological cardiac hypertrophy. In cultured cardiomyocytes, transcription factor Gata4 required for agonist-induced We hypothesized that, intact organism, an regulator postnatal function and hypertrophic response to stress. To test this hypothesis, we studied mice heterozygous deletion second exon ( G4D ). At baseline, had mild systolic diastolic dysfunction associated with reduced weight decreased cardiomyocyte number. After transverse aortic constriction (TAC), developed overt eccentric hypertrophy, significantly increased fibrosis apoptosis. Inhibition apoptosis by overexpression insulin-like growth 1 receptor prevented TAC-induced mice. Unlike WT-TAC controls, -TAC cardiomyocytes hypertrophied increasing length more than width. Gene expression profiling revealed up-regulation genes fibrosis, including members TGF-β pathway. Our data demonstrate that essential heart. pressure overload, regulates pattern hypertrophy protects from load-induced failure.