Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling.
| Title: | Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling. |
|---|---|
| Authors: | Gupta MK; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. manveenkgupta@yahoo.com.; Sahu A; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Sun Y; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Mohan ML; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Kumar A; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Zalavadia A; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Wang X; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Martelli EE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Stenson K; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Witherow CP; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Drazba J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Dasarathy S; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.; Naga Prasad SV; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. prasads2@ccf.org. |
| Source: | Scientific reports [Sci Rep] 2021 Nov 10; Vol. 11 (1), pp. 22018. Date of Electronic Publication: 2021 Nov 10. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| MeSH Terms: | Ventricular Remodeling*; Cardiomegaly/*diagnostic imaging ; MicroRNAs/*metabolism ; Myocytes, Cardiac/*metabolism; Aorta, Thoracic/surgery ; ErbB Receptors/metabolism ; Ligation/methods ; Membrane Proteins/metabolism ; MicroRNAs/genetics ; Mitochondrial Membranes/metabolism ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Animals ; Echocardiography ; Mice, Transgenic |
| 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.; (© 2021. The Author(s).) |
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| Grant Information: | S10 OD021561 United States OD NIH HHS; S10 OD023436 United States OD NIH HHS; 10POST3610049 American Heart Association; SIG 1S10ODO21561 United States NH NIH HHS |
| Substance Nomenclature: | EC 2.7.10.1 (ErbB Receptors); 0 (Membrane Proteins); 0 (MicroRNAs); EC 2.7.10.1 (Erb-b2 Receptor Tyrosine Kinases); 0 (MIRN7 microRNA, mouse) |
| Entry Date(s): | Date Created: 20211111 Date Completed: 20220126 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8581024 |
| DOI: | 10.1038/s41598-021-00778-6 |
| PMID: | 34759299 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't