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Transcriptional regulation of structural and functional adaptations in a developing adulthood myocardium

Sini Sunny, Anil Kumar Challa, Joseph Barchue, Muralidharan T. Ramamurthy, David K Crossman, Steven Pogwizd, Senthilkumar Cinghu, Namakkal S. Rajasekaran
doi: https://doi.org/10.1101/2020.11.25.397885
Sini Sunny
aCardiac Aging & Redox Signaling Laboratory, Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
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Anil Kumar Challa
aCardiac Aging & Redox Signaling Laboratory, Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
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Joseph Barchue
bComprehensive Cardiovascular Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Muralidharan T. Ramamurthy
cDepartment of Cardiology, Sri Ramachandra Medical University & Research Institute, Chennai, India
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David K Crossman
dDepartment of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
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Steven Pogwizd
bComprehensive Cardiovascular Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Senthilkumar Cinghu
eEpigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
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Namakkal S. Rajasekaran
aCardiac Aging & Redox Signaling Laboratory, Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
fDivision of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, UT, USA
gCenter for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA
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  • For correspondence: rajnsr@uabmc.edu
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Abstract

The development of the heart follows a synergic action of several signaling pathways during gestational, pre- & postnatal stages. The current study aimed to investigate whether the myocardium experiences transcriptional changes during the transition from post-natal to adult hood stages. Herein, we used C57/Bl6/J mice at 4 (28-days; post-natal/PN) and 20 weeks (adulthood/AH) of ages and employed the next generation RNAseq (NGS) to profile the transcriptome and echocardiography analysis to monitor the structural/functional changes in the heart. NGS-based RNA-seq revealed that 1215 genes were significantly upregulated and 2549 were down regulated in the AH versus PN hearts, indicating a significant transcriptional change during this transition. A synchronized cardiac transcriptional regulation through cell cycle, growth hormones, redox homeostasis and metabolic pathways was noticed in both PN and AH hearts. Echocardiography reveals significant structural and functional (i.e. systolic/diastolic) changes during the transition of PN to adult stage. Particularly, a progressive decline in ejection fraction (EF) and cardiac output was observed in AH hearts. These structural adaptations are in line with critical signaling pathways that drive the maturation of heart during AH. Overall, we have presented a comprehensive transcriptomic analysis along with structural-functional relationship during the myocardial development in adult mice.

Competing Interest Statement

The authors have declared no competing interest.

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Posted November 27, 2020.
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Transcriptional regulation of structural and functional adaptations in a developing adulthood myocardium
Sini Sunny, Anil Kumar Challa, Joseph Barchue, Muralidharan T. Ramamurthy, David K Crossman, Steven Pogwizd, Senthilkumar Cinghu, Namakkal S. Rajasekaran
bioRxiv 2020.11.25.397885; doi: https://doi.org/10.1101/2020.11.25.397885
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Transcriptional regulation of structural and functional adaptations in a developing adulthood myocardium
Sini Sunny, Anil Kumar Challa, Joseph Barchue, Muralidharan T. Ramamurthy, David K Crossman, Steven Pogwizd, Senthilkumar Cinghu, Namakkal S. Rajasekaran
bioRxiv 2020.11.25.397885; doi: https://doi.org/10.1101/2020.11.25.397885

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