Transcriptomics,Multiomics

Dataset Information

4

Transcription profiling of hearts from mice heterozygous for Gata4 mutation (G4D) to investigate the significance of Gata4 in regulating postnatal heart function and in regulating the hypertrophic response of the heart to pathological stress.


ABSTRACT: 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. Experiment 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 Experiment Overall Design: overload.

OTHER RELATED OMICS DATASETS IN: PRJNA96145

INSTRUMENT(S): 418 [Affymetrix]

SUBMITTER: Sek Won Kong  

PROVIDER: E-GEOD-5500 | ArrayExpress | 2007-11-13

SECONDARY ACCESSION(S): GDS2316GSE5500PRJNA96145

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-5500.idf.txt Idf
E-GEOD-5500.processed.1.zip Processed
E-GEOD-5500.raw.1.zip Raw
E-GEOD-5500.sdrf.txt Txt
Items per page:
1 - 4 of 4
altmetric image

Publications

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

Bisping Egbert E   Ikeda Sadakatsu S   Kong Sek Won SW   Tarnavski Oleg O   Bodyak Natalya N   McMullen Julie R JR   Rajagopal Satish S   Son Jennifer K JK   Ma Qing Q   Springer Zhangli Z   Kang Peter M PM   Izumo Seigo S   Pu William T WT  

Proceedings of the National Academy of Sciences of the United States of America 20060918 39


An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiomyocytes, the transcription factor Gata4 is required for agonist-induced 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 bas  ...[more]

Similar Datasets

2006-01-01 | S-EPMC1636702 | BioStudies
| GSE5500 | GEO
2017-01-01 | S-EPMC5286367 | BioStudies
2019-01-01 | S-EPMC6877536 | BioStudies
2016-01-01 | S-EPMC4767297 | BioStudies
2011-01-01 | S-EPMC3145698 | BioStudies
1000-01-01 | S-EPMC2843206 | BioStudies
2017-01-01 | S-EPMC5707145 | BioStudies
2014-01-01 | S-EPMC4300109 | BioStudies
1000-01-01 | S-EPMC2662553 | BioStudies