Imperial College London
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Dr Fu Siong Ng

Faculty of Medicine, National Heart & Lung Institute

Reader in Cardiac Electrophysiology
 
 
 
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Contact

 

+44 (0)20 7594 3614f.ng Website

 
 
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Location

 

430ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rutledge:2014:10.1016/j.jacc.2013.10.081,
author = {Rutledge, CA and Ng, FS and Sulkin, MS and Greener, ID and Sergeyenko, AM and Liu, H and Gemel, J and Beyer, EC and Sovari, AA and Efimov, IR and Dudley, SC},
doi = {10.1016/j.jacc.2013.10.081},
journal = {Journal of the American College of Cardiology},
pages = {928--934},
title = {c-Src kinase inhibition reduces arrhythmia inducibility and connexin43 dysregulation after myocardial infarction},
url = {http://dx.doi.org/10.1016/j.jacc.2013.10.081},
volume = {63},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectivesThe aim of this study was to evaluate the role of tyrosine kinase cellular-Src (c-Src) inhibition on connexin43 (Cx43) regulation in a mouse model of myocardial infarction (MI).BackgroundMI is associated with decreased expression of Cx43, the principal gap junction protein responsible for propagating current in ventricles. Activated c-Src has been linked to Cx43 dysregulation.MethodsMI was induced in 12-week-old mice by coronary artery occlusion. MI mice were treated with c-Src inhibitors (PP1 or AZD0530), PP3 (an inactive analogue of PP1), or saline. Treated hearts were compared to sham mice by echocardiography, optical mapping, telemetry electrocardiographic monitoring, and inducibility studies. Tissues were collected for immunoblotting, quantitative polymerase chain reaction, and immunohistochemistry.ResultsActive c-Src was elevated in PP3-treated MI mice compared to sham at the scar border (280%, p = 0.003) and distal ventricle (346%, p = 0.013). PP1 treatment restored active c-Src to sham levels at the scar border (86%, p = 0.95) and distal ventricle (94%, p = 1.0). PP1 raised Cx43 expression by 69% in the scar border (p = 0.048) and by 73% in the distal ventricle (p = 0.043) compared with PP3 mice. PP1-treated mice had restored conduction velocity at the scar border (PP3: 32 cm/s, PP1: 41 cm/s, p < 0.05) and lower arrhythmic inducibility (PP3: 71%, PP1: 35%, p < 0.05) than PP3 mice. PP1 did not change infarct size, electrocardiographic pattern, or cardiac function. AZD0530 treatment demonstrated restoration of Cx43 comparable to PP1.Conclusionsc-Src inhibition improved Cx43 levels and conduction velocity and lowered arrhythmia inducibility after MI, suggesting a new approach for arrhythmia reduction following MI.
AU  - Rutledge,CA
AU  - Ng,FS
AU  - Sulkin,MS
AU  - Greener,ID
AU  - Sergeyenko,AM
AU  - Liu,H
AU  - Gemel,J
AU  - Beyer,EC
AU  - Sovari,AA
AU  - Efimov,IR
AU  - Dudley,SC
DO  - 10.1016/j.jacc.2013.10.081
EP  - 934
PY  - 2014///
SN  - 0735-1097
SP  - 928
TI  - c-Src kinase inhibition reduces arrhythmia inducibility and connexin43 dysregulation after myocardial infarction
T2  - Journal of the American College of Cardiology
UR  - http://dx.doi.org/10.1016/j.jacc.2013.10.081
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000332399700012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S0735109713064929?via%3Dihub
VL  - 63
ER  -
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