TWEAK promotes endothelial progenitor cell vasculogenesis to alleviate acute myocardial infarction via the Fn14-NF-κB signaling pathway.

Abstract

Acute myocardial infarction (AMI) remains one of the leading causes of mortality worldwide; however, endothelial progenitor cell (EPC) transplantation has been proposed as a promising treatment strategy for EPC. High levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) have been reported in AMI, although its effect on EPCs has not been reported. In the present study, immunofluorescence and flow cytometry were performed to assess the effect of TWEAK in isolated mouse EPCs. Echocardiography was used to evaluate the cardiac function of murine hearts following EPC treatment in the AMI model, while collagen synthesis within the heart tissue was assessed using Masson's trichrome staining. A tube formation assay and Transwell migration assay were performed to investigate the effects of TWEAK on vessel formation and EPC migration in vitro. Angiogenesis and arteriogenesis were assessed in vivo using immunohistochemistry and western blotting was performed to determine the effect of TWEAK-mediated nuclear factor (NF)-κB pathway activation in EPCs. The results revealed that TWEAK promotes EPC migration, tube formation and viability in vitro. Furthermore, TWEAK treatment resulted in improved cardiac function, decreased heart collagen and vasculogenesis in mice with AMI, which was mediated by the TWEAK- fibroblast growth factor-inducible 14 (Fn14)-NF-κB signaling pathway, as determined using Fn14 small interfering (si)RNA and Bay 11-7082 (an NF-κB inhibitor). In summary, the results of the present study suggest that activation of the TWEAK-Fn14-NF-κB signaling pathway exerts a beneficial effect on EPCs for the treatment of AMI.

• Authors: Zulong Sheng, Chenwei Ju, Bing Li, Zhongpu Chen, Xiaodong Pan, Gaoliang Yan, Yanru He, Yuyu Yao, Genshan Ma
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 16 Issue 5 Pg. 4019-4029 (Nov 2018) ISSN: 1792-0981 [Print] Greece
• PMID: 30344680 (Publication Type: Journal Article)