cTnI Exacerbates Myocardial Ischemia/Reperfusion Injury by Inducing Adhesion of Monocytes to VECs via TLR4/NF-{kappa}B-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 ischemia-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 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 NF-B were involved in the signaling pathway, because blockade of either TLR4 or NF-B 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...

Source: Clinical Science - September 27, 2016 Category: Biomedical Science Authors: Han, Y., Liao, X., Gao, Z., Yang, S., Chen, C., Liu, Y., Wang, W. E., Wu, G., Chen, X., Jose, P. A., Zhang, Y., Zeng, C. Tags: PublishAheadOfPrint Source Type: research