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Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart

Item Type:Article
Title:Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart
Creators Name:Queiros, A.M., Eschen, C., Fliegner, D., Kararigas, G., Dworatzek, E., Westphal, C., Sanchez Ruderisch, H. and Regitz-Zagrosek, V.
Abstract:BACKGROUND: In pressure overload, profibrotic gene expression and cardiac fibrosis are more pronounced in males than in females. Sex-specific and estrogen-dependent regulation of microRNAs (miRNAs), such as miR-21, may be a potential mechanism leading to sex differences in fibrosis. OBJECTIVES: To analyze the influence of sex, estrogen, and estrogen receptor {beta} (ER{beta}) on the expression of miR-21 and to identify additional miRNAs potentially involved in sex-specific pressure overload-induced cardiac remodeling. METHODS: The sex-specific regulation of fibrosis-related miRNAs was analyzed in male and female wild type and ER{beta}-deficient mice after transverse aortic constriction (TAC), in rat fibroblasts, and in a cardiomyocyte-like cell line. RESULTS: We report the sex-specific expression of functionally-related miR-21, -24, -27a, -27b, 106a, -106b and the regulation of their expression by estrogen in a sex-specific manner. These effects were abolished in ER{beta}-deficient mice. We demonstrate the presence of common functional target sites for these miRNAs on three repressors of the mitogen-activated protein kinase signaling pathway, i.e. Rasa1, Rasa2 and Spry1, which may all lead to cardiac fibrosis. As expected, transfection with miRNA mimics targeting these repressors induced ERK1/2 phosphorylation. CONCLUSIONS: Estrogen regulates a network of miRNAs in a sex-specific manner via ER{beta}. Our data suggest that the sex-specific expression of these miRNAs may be related to sex differences in fibrosis after pressure overload.
Keywords:miRNAs, Estradiol, Sex-Specific, Hypertrophy, Estrogen Receptor {beta}, Animals, Mice, Rats
Source:International Journal of Cardiology
Page Range:331-338
Date:20 November 2013
Official Publication:https://doi.org/10.1016/j.ijcard.2013.09.002
PubMed:View item in PubMed

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