Cardiac troponin I (cTnI), a biomarker for myocardial damage and risk stratification, may be involved in the pathogenesis of cardiovascular diseases, which was ascribed to the effect of cTnI auto-antibodies. Whether or not cTnI itself has a direct impact on acute myocardial injury is unknown. To exclude the influence of cTnI antibody on the cardiac infarct size, we studied the effect of cTnI shortly after myocardial ischaemia–reperfusion (I/R) injury when cTnI antibodies were not elevated. Pretreatment with cTnI augmented the myocardial infarct size caused by I/R, accompanied by an increase in inflammatory markers in the blood and myocardium. Additional experiments using human umbilical vein endothelial cells (HUVECs) showed that the detrimental effect of cTnI was related to cTnI-induced increase in vascular cell adhesion molecule-1 (VCAM-1) expression and VCAM-1 mediated adhesion of human monocytes (THP-1) to HUVECs, which could be neutralized by VCAM-1 antibody. Both toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were involved in the signalling pathway, because blockade of either TLR4 or NF-κB inhibited the cTnI's effect on VCAM-1 expression and adhesion of monocytes to endothelial cells. Moreover, TLR4 inhibition reduced cTnI-augmented cardiac injury in rats with I/R injury. We conclude that cTnI exacerbates myocardial I/R injury by inducing the adhesion of monocytes to vascular endothelial cells via activation of the TLR4/NF-κB pathway. Inhibition of TLR4 may be an alternative strategy to reduce cTnI-induced myocardial I/R injury.
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IL-13 induced actin cytoskeleton rearrangement in human podocytes. Magnification, x60, scale bar, 20μm. For more information please see pp. 2317-2327. Image provided by Chan Chang Yien.
Research Article|
November 10 2016
Cardiac troponin I exacerbates myocardial ischaemia/reperfusion injury by inducing the adhesion of monocytes to vascular endothelial cells via a TLR4/NF-κB-dependent pathway
Yu Han;
Yu Han
1
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Xiang Liao;
Xiang Liao
1
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Zhao Gao;
Zhao Gao
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Sufei Yang;
Sufei Yang
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Caiyu Chen;
Caiyu Chen
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Yukai Liu;
Yukai Liu
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Wei Eric Wang;
Wei Eric Wang
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Gengze Wu;
Gengze Wu
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
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Xiongwen Chen;
Xiongwen Chen
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
‡Cardiovascular Research Center & Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Pedro A. Jose;
Pedro A. Jose
§Department of Medicine, Division of Renal Disease and Hypertension, The George Washington University School of Medicine & Health Sciences, Washington D.C., 20037, U.S.A.
║Department of Pharmacology and Physiology, The George Washington University School of Medicine & Health Sciences, Washington D.C., 20037, U.S.A.
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Ye Zhang;
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
Correspondence: Chunyu Zeng (email [email protected]) or Ye Zhang (email [email protected])
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Chunyu Zeng
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China
†Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China
Correspondence: Chunyu Zeng (email [email protected]) or Ye Zhang (email [email protected])
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Publisher: Portland Press Ltd
Received:
April 08 2016
Revision Received:
June 29 2016
Accepted:
September 28 2016
Accepted Manuscript online:
September 28 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (24): 2279–2293.
Article history
Received:
April 08 2016
Revision Received:
June 29 2016
Accepted:
September 28 2016
Accepted Manuscript online:
September 28 2016
Connected Content
This is a commentary on:
Does extracellular cardiac troponin I play a pathogenic role independently of autoantibodies?
Citation
Yu Han, Xiang Liao, Zhao Gao, Sufei Yang, Caiyu Chen, Yukai Liu, Wei Eric Wang, Gengze Wu, Xiongwen Chen, Pedro A. Jose, Ye Zhang, Chunyu Zeng; Cardiac troponin I exacerbates myocardial ischaemia/reperfusion injury by inducing the adhesion of monocytes to vascular endothelial cells via a TLR4/NF-κB-dependent pathway. Clin Sci (Lond) 1 December 2016; 130 (24): 2279–2293. doi: https://doi.org/10.1042/CS20160373
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