Imperial College London

ProfessorMichaelSchneider

Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology
 
 
 
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Contact

 

+44 (0)013 34621727m.d.schneider Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shukla:2011:10.1038/ncomms1601,
author = {Shukla, PC and Singh, KK and Quan, A and Al-Omran, M and Teoh, H and Lovren, F and Cao, L and Rovira, II and Pan, Y and Brezden-Masley, C and Yanagawa, B and Gupta, A and Deng, C-X and Coles, JG and Leong-Poi, H and Stanford, WL and Parker, TG and Schneider, MD and Finkel, T and Verma, S},
doi = {10.1038/ncomms1601},
journal = {Nature Communications},
pages = {1--11},
title = {BRCA1 is an essential regulator of heart function and survival following myocardial infarction},
url = {http://dx.doi.org/10.1038/ncomms1601},
volume = {2},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer but its role in protecting other tissues from DNA damage has not been explored. Here we show a new role for BRCA1 as a gatekeeper of cardiac function and survival. In mice, loss of BRCA1 in cardiomyocytes results in adverse cardiac remodelling, poor ventricular function and higher mortality in response to ischaemic or genotoxic stress. Mechanistically, loss of cardiomyocyte BRCA1 results in impaired DNA double-strand break repair and activated p53-mediated pro-apoptotic signalling culminating in increased cardiomyocyte apoptosis, whereas deletion of the p53 gene rescues BRCA1-deficient mice from cardiac failure. In human adult and fetal cardiac tissues, ischaemia induces double-strand breaks and upregulates BRCA1 expression. These data reveal BRCA1 as a novel and essential adaptive response molecule shielding cardiomyocytes from DNA damage, apoptosis and heart dysfunction. BRCA1 mutation carriers, in addition to risk of breast and ovarian cancer, may be at a previously unrecognized risk of cardiac failure.
AU - Shukla,PC
AU - Singh,KK
AU - Quan,A
AU - Al-Omran,M
AU - Teoh,H
AU - Lovren,F
AU - Cao,L
AU - Rovira,II
AU - Pan,Y
AU - Brezden-Masley,C
AU - Yanagawa,B
AU - Gupta,A
AU - Deng,C-X
AU - Coles,JG
AU - Leong-Poi,H
AU - Stanford,WL
AU - Parker,TG
AU - Schneider,MD
AU - Finkel,T
AU - Verma,S
DO - 10.1038/ncomms1601
EP - 11
PY - 2011///
SN - 2041-1723
SP - 1
TI - BRCA1 is an essential regulator of heart function and survival following myocardial infarction
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/ncomms1601
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299159900025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.nature.com/articles/ncomms1601
UR - http://hdl.handle.net/10044/1/82363
VL - 2
ER -