Document Detail


Transcriptome characterization of estrogen-treated human myocardium identifies Myosin regulatory light chain interacting protein as a sex-specific element influencing contractile function.
MedLine Citation:
PMID:  22261164     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: This study investigated the effects of 17β-estradiol (E2) on gene regulation in human cardiac tissues. We hypothesized that a candidate E2 effect is cardiomyocyte (CM)- and sex-specific, conserved between humans and mice, and that E2 impairs contractile function in male CMs only.
BACKGROUND: Both men and women produce E2 locally from androgenic precursors. E2 regulates cardiovascular function, but specific mechanisms, protective or harmful, are not fully understood.
METHODS: We performed genome-wide expression profiling of E2-treated cardiac tissues from men and women, and studied gene expression and function in CMs from hearts of male and female E2-treated mice.
RESULTS: We found 36 E2-dependent genes regulated in a sex-specific manner. Of these, after E2 exposure, the myosin regulatory light chain interacting protein (MYLIP) gene was induced in tissues of men only. Focusing on Mylip and employing isolated mouse CMs, we confirmed our hypotheses that the E2 effect is CM- and sex-specific and conserved between humans and mice. The E2-treatment led to impaired contractile function in male CMs only, which was characterized by increased Mylip mRNA and protein levels, and decreased myosin regulatory light chain (Mrlc) protein. Our report is the first to our knowledge to show that cardiac Mrlc is an in vivo substrate for Mylip, leading to augmented Mrlc ubiquitination. Of relevance, we found that MYLIP expression levels rise with increasing age in hearts of men.
CONCLUSIONS: E2 directly influences cardiac gene regulation, and E2 actions may be different between the sexes. Since E2 levels rise in older and/or obese men, pharmacological targeting of MYLIP in men with elevated E2 levels could possibly decrease their risk for the development or progression of cardiovascular disease.
Authors:
Georgios Kararigas; Virginie Bito; Hanna Tinel; Eva Becher; Istvan Baczko; Christoph Knosalla; Barbara Albrecht-Küpper; Karin R Sipido; Vera Regitz-Zagrosek
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  59     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  410-7     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Institute of Gender in Medicine and Center for Cardiovascular Research, Charite University Hospital, Berlin, Germany.
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