Imperial College London
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Professor Thanos Athanasiou MD PhD MBA FECTS FRCS

Faculty of Medicine, Department of Surgery & Cancer

Professor of Cardiovascular Sciences
 
 
 
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Contact

 

t.athanasiou

 
 
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Location

 

1022Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Naase:2020:10.1186/s13019-020-01179-y,
author = {Naase, H and Harling, L and Kidher, E and Sepehripour, A and Nguyen, B and Kapelouzou, A and Cokkinos, D and Angelini, G and Evans, P and Athanasiou, T},
doi = {10.1186/s13019-020-01179-y},
journal = {Journal of Cardiothoracic Surgery},
title = {Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass},
url = {http://dx.doi.org/10.1186/s13019-020-01179-y},
volume = {15},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectivesCardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6).Materials and methodsThe role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model.ResultsIn the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB).ConclusionCPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflam
AU  - Naase,H
AU  - Harling,L
AU  - Kidher,E
AU  - Sepehripour,A
AU  - Nguyen,B
AU  - Kapelouzou,A
AU  - Cokkinos,D
AU  - Angelini,G
AU  - Evans,P
AU  - Athanasiou,T
DO  - 10.1186/s13019-020-01179-y
PY  - 2020///
SN  - 1749-8090
TI  - Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass
T2  - Journal of Cardiothoracic Surgery
UR  - http://dx.doi.org/10.1186/s13019-020-01179-y
UR  - http://hdl.handle.net/10044/1/80033
VL  - 15
ER  -
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