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

Authors: Queiros, AM  Eschen, C  Fliegner, D  Kararigas, G  Dworatzek, E  Westphal, C  Sanchez Ruderisch, H  Regitz-Zagrosek, V 
Citation: Queiros AM, etal., Int J Cardiol. 2013 Nov 20;169(5):331-8. doi: 10.1016/j.ijcard.2013.09.002. Epub 2013 Oct 5.
Pubmed: (View Article at PubMed) PMID:24157234
DOI: Full-text: DOI:10.1016/j.ijcard.2013.09.002

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 (ERbeta) 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 ERbeta-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 ERbeta-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 ERbeta. Our data suggest that the sex-specific expression of these miRNAs may be related to sex differences in fibrosis after pressure overload.


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CRRD Object Information
CRRD ID: 9999450
Created: 2015-04-21
Species: All species
Last Modified: 2015-04-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.