Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α

Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10-12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.

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Publication Details

Journal
npj Metabolic Health and Disease
Published
2024-11-06
DOI
https://doi.org/10.1038/s44324-024-00033-2
Citations
1
Primary Topic
Cardiac Fibrosis and Remodeling
Type
article
Field-Weighted Citation Impact
0.40

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article

Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α

James R. Bell, Victoria C. Garside, Lea M.D. Delbridge, Helen Kiriazis et al.
1 citations
npj Metabolic Health and Disease
Cardiac Fibrosis and Remodeling
0.40
article

Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α

James R. Bell, Victoria C. Garside, Lea M.D. Delbridge, Helen Kiriazis, Kate L. Weeks, Kimberley M. Mellor, A. Raaijmakers, Adam J. Trewin, Julie R. McMullen, D. Donner, K. A. Smith, Nicola M. Sergienko
article en
1 citations

Abstract

Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10-12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.

npj Metabolic Health and DiseaseVol. 2(1)
Baker Heart and Diabetes Institute (AU), University of Auckland (NZ), The University of Melbourne (AU), La Trobe University (AU), Monash Alfred Psychiatry Research centre (AU), Melbourne Health (AU), Monash University (AU)
Baker Foundation, Australian Government, National Heart Foundation of Australia, Medical Research Council, National Health and Medical Research Council
Openalex Percentile: Top 31%
Cardiac Fibrosis and Remodeling
0.40
DOIOpen Access PDFOpenAlex
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