Gupta 2021 Sci Rep

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Gupta MK, Sahu A, Sun Y, Mohan ML, Kumar A, Zalavadia A, Wang X, Martelli EE, Stenson K, Witherow CP, Drazba J, Dasarathy S, Naga Prasad SV (2021) Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling. Sci Rep 11:22018.

» PMID: 34759299 Open Access

Gupta MK, Sahu A, Sun Y, Mohan ML, Kumar A, Zalavadia A, Wang X, Martelli EE, Stenson K, Witherow CP, Drazba J, Dasarathy S, Naga Prasad SV (2021) Sci Rep

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.

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2021-11