Human cytomegalovirus promotes the activation of TGF-β1 in human umbilical vein endothelial cells by MMP-2 after endothelial mesenchymal transition.

BACKGROUND

Human cytomegalovirus (HCMV) infection is one of the risk factors of cardiovascular disease; the most important pathological change is the change of vascular endothelial cell (VEC) function, but its mechanism is still unclear. Transforming growth factor β1 (TGF-β1) is an important cytokine associated with fibrosis; it can induce the occurrence of endothelial mesenchymal transition (EndMT) in VECs, which means endothelial cells acquire the characteristics and phenotypes of mesenchymal cells and secrete molecules associated with the deposition and remodeling of the extracellular matrix. Many in vivo and in vitro studies have shown that HCMV infection promotes the secretion and activation of TGF-β1.

OBJECTIVES

This study aims to observe the changes of endothelial cells after HCMV infection and EndMT occurrence induced by TGF-β1 and to explore the possible mechanism of HCMV infection in the pathogenesis of cardiovascular disease.

MATERIAL AND METHODS

Immunofluorescence staining, reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation methods were used in this study to analyze the changes in morphology and gene expression.

RESULTS

We found that EndMT-related morphological and gene expression changes occurred in human umbilical vein endothelial cells (HUVECs) infected and uninfected with HCMV after treatment with TGF-β1. Human umbilical vein endothelial cells infected with HCMV, which are treated with TGF-β1, can activate the extracellular potential TGF-β1 by activating matrix metalloproteinase 2 (MMP-2).

CONCLUSIONS

Our findings provide a molecular basis for the association between HCMV infection, TGF-β1 and cardiovascular disease.