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Series GSE5500 Query DataSets for GSE5500
Status Public on Aug 12, 2006
Title Gata4 is required for postnatal cardiac function and protection from pressure overload-induced heart failure
Organism Mus musculus
Experiment type Expression profiling by array
Summary An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiac cardiomyocytes, the transcription factor Gata4 is required for agonist-induced cardiomyocyte hypertrophy. We hypothesized that in the intact organism Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed upregulation of genes associated with apoptosis and
fibrosis, including members of the TGF? pathway. Our data demonstrate that Gata4 is essential for cardiac function in the postnatal heart. After pressure overload, Gata4 regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure.
Keywords: genetic modification, pressure overload stress response
Overall design We reasoned that if Gata4 was a crucial regulator of pathways necessary for cardiac hypertrophy, then modest reductions of Gata4 activity should result in an observable cardiac phenotype. To test this hypothesis, we used gene targeted mice that express reduced levels of Gata4. We characterized these mice at baseline and after pressure
Contributor(s) Bisping E, Ikeda S, Kong S, Tarnavski O, Bodyak N, McMullen JR, Rajagopal S, Son JK, Ma Q, Springer Z, Kang PM, Izumo S, Pu WT
Citation(s) 16983087
Submission date Aug 10, 2006
Last update date Feb 11, 2019
Contact name Sek Won Kong
Phone 617-919-2689
Organization name Boston Children's Hospital
Department Informatics Program
Lab EN137
Street address 300 Longwood Avenue
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (21)
GSM126895 Wildtype_Sham_Rep1
GSM126898 Wildtype_Sham_Rep2
GSM126901 Wildtype_Sham_Rep3
BioProject PRJNA96145

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GSE5500_RAW.tar 132.2 Mb (http)(custom) TAR (of CEL)

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