Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ERbeta attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure.
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
Sex, Age, Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression underlying cardiac development by HDAC2 and identified distinct classes of up-regulated and down-regulated genes during this process.
Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity.
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View SamplesPressure overload (PO) leads first to cardiac hypertrophy and later to heart failure. In mice, PO leads to sex differences in cardiac morphology and function. However, early sex differences in gene regulation that precede sex differences in function have not yet been identified.
Sex-specific pathways in early cardiac response to pressure overload in mice.
Sex
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CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in Cancer Patients.
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View SamplesFoxO6 is expressed in the brain, craniofacial region and somite, but the precise role of FoxO6 in craniofacial development remain unknown. We found that FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull.
FoxO6 regulates Hippo signaling and growth of the craniofacial complex.
Specimen part
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