Imperial College London
Alternate

ProfessorVaniaBraga

Faculty of Medicine, National Heart & Lung Institute

Professor of Cellular Signalling
 
 
 
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Contact

 

+44 (0)20 7594 3233v.braga

 
 
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Location

 

Office no. 105Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Schultz:2019:10.1096/fj.201802740RR,
author = {Schultz, F and Swiatlowska, P and Alvarez-Laviada, A and Sanchez-Alonso, JL and Song, Q and de, Vries AAF and Pijnappels, DA and Ongstad, E and Braga, VMM and Entcheva, E and Gourdie, RG and Miragoli, M and Gorelik, J},
doi = {10.1096/fj.201802740RR},
journal = {FASEB Journal},
pages = {1--16},
title = {Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43.},
url = {http://dx.doi.org/10.1096/fj.201802740RR},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Healthy cardiomyocytes are electrically coupled at the intercalated discs by gap junctions. In infarcted hearts, adverse gap-junctional remodeling occurs in the border zone, where cardiomyocytes are chemically and electrically influenced by myofibroblasts. The physical movement of these contacts remains unquantified. Using scanning ion conductance microscopy, we show that intercellular contacts between cardiomyocytes and myofibroblasts are highly dynamic, mainly owing to the edge dynamics (lamellipodia) of the myofibroblasts. Decreasing the amount of functional connexin-43 (Cx43) at the membrane through Cx43 silencing, suppression of Cx43 trafficking, or hypoxia-induced Cx43 internalization attenuates heterocellular contact dynamism. However, we found decreased dynamism and stabilized membrane contacts when cellular coupling was strengthened using 4-phenylbutyrate (4PB). Fluorescent-dye transfer between cells showed that the extent of functional coupling between the 2 cell types correlated with contact dynamism. Intercellular calcein transfer from myofibroblasts to cardiomyocytes is reduced after myofibroblast-specific Cx43 down-regulation. Conversely, 4PB-treated myofibroblasts increased their functional coupling to cardiomyocytes. Consistent with lamellipodia-mediated contacts, latrunculin-B decreases dynamism, lowers physical communication between heterocellular pairs, and reduces Cx43 intensity in contact regions. Our data show that heterocellular cardiomyocyte-myofibroblast contacts exhibit high dynamism. Therefore, Cx43 is a potential target for prevention of aberrant cardiomyocyte coupling and myofibroblast proliferation in the infarct border zone.-Schultz, F., Swiatlowska, P., Alvarez-Laviada, A., Sanchez-Alonso, J. L., Song, Q., de Vries, A. A. F., Pijnappels, D. A., Ongstad, E., Braga, V. M. M., Entcheva, E., Gourdie, R. G., Miragoli, M., Gorelik, J. Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43.
AU  - Schultz,F
AU  - Swiatlowska,P
AU  - Alvarez-Laviada,A
AU  - Sanchez-Alonso,JL
AU  - Song,Q
AU  - de,Vries AAF
AU  - Pijnappels,DA
AU  - Ongstad,E
AU  - Braga,VMM
AU  - Entcheva,E
AU  - Gourdie,RG
AU  - Miragoli,M
AU  - Gorelik,J
DO  - 10.1096/fj.201802740RR
EP  - 16
PY  - 2019///
SN  - 0892-6638
SP  - 1
TI  - Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43.
T2  - FASEB Journal
UR  - http://dx.doi.org/10.1096/fj.201802740RR
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31253057
UR  - https://www.fasebj.org/doi/10.1096/fj.201802740RR
ER  -
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