Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

Abstract Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to...

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Autores principales: Manveen K. Gupta, Anita Sahu, Yu Sun, Maradumane L. Mohan, Avinash Kumar, Ajaykumar Zalavadia, Xi Wang, Elizabeth E. Martelli, Kate Stenson, Conner P. Witherow, Judy Drazba, Srinivasan Dasarathy, Sathyamangla V. Naga Prasad
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/51f839007800465793b14c9b05827ac8
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spelling oai:doaj.org-article:51f839007800465793b14c9b05827ac82021-11-14T12:22:21ZCardiac expression of microRNA-7 is associated with adverse cardiac remodeling10.1038/s41598-021-00778-62045-2322https://doaj.org/article/51f839007800465793b14c9b05827ac82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00778-6https://doaj.org/toc/2045-2322Abstract Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.Manveen K. GuptaAnita SahuYu SunMaradumane L. MohanAvinash KumarAjaykumar ZalavadiaXi WangElizabeth E. MartelliKate StensonConner P. WitherowJudy DrazbaSrinivasan DasarathySathyamangla V. Naga PrasadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Manveen K. Gupta
Anita Sahu
Yu Sun
Maradumane L. Mohan
Avinash Kumar
Ajaykumar Zalavadia
Xi Wang
Elizabeth E. Martelli
Kate Stenson
Conner P. Witherow
Judy Drazba
Srinivasan Dasarathy
Sathyamangla V. Naga Prasad
Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
description Abstract Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.
format article
author Manveen K. Gupta
Anita Sahu
Yu Sun
Maradumane L. Mohan
Avinash Kumar
Ajaykumar Zalavadia
Xi Wang
Elizabeth E. Martelli
Kate Stenson
Conner P. Witherow
Judy Drazba
Srinivasan Dasarathy
Sathyamangla V. Naga Prasad
author_facet Manveen K. Gupta
Anita Sahu
Yu Sun
Maradumane L. Mohan
Avinash Kumar
Ajaykumar Zalavadia
Xi Wang
Elizabeth E. Martelli
Kate Stenson
Conner P. Witherow
Judy Drazba
Srinivasan Dasarathy
Sathyamangla V. Naga Prasad
author_sort Manveen K. Gupta
title Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
title_short Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
title_full Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
title_fullStr Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
title_full_unstemmed Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling
title_sort cardiac expression of microrna-7 is associated with adverse cardiac remodeling
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/51f839007800465793b14c9b05827ac8
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