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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Nature Portfolio
2021
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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) |
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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 |
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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 |
work_keys_str_mv |
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