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.
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.
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.
Yu
Y
Han
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.
Xiang
X
Liao
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.
Zhao
Z
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.
Sufei
S
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.
Caiyu
C
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.
Yukai
Y
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.
Wei Eric
WE
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.
Gengze
G
Wu
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.
Xiongwen
X
Chen
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.
Pedro A
PA
Jose
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China cyzeng1@hotmail.com) whiteyezi@163.com.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China.
Ye
Y
Zhang
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, P.R. China cyzeng1@hotmail.com) whiteyezi@163.com.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, 400042, P.R. China.
Chunyu
C
Zeng
adhesion factor; cardiac troponin I; coronary heart disease; endothelial cell; myocardial ischaemia–reperfusion injury