Human cytomegalovirus promoting endothelial cell proliferation by targeting regulator of G-protein signaling 5 hypermethylation and downregulation

Xiaoni Zhang,Yongmin Liu,Na Tang,Dongmei Xi,Qian Feng,Lamei Wang,Fang He,Hua Zhong,Yan Tang

doi:10.1038/s41598-020-58680-6

Abstract

Interactions between human cytomegalovirus (HCMV) infection and environmental factors can increase susceptibility to essential hypertension (EH). Although endothelial dysfunction is the initial factor of EH, the epigenetic mechanisms through which HCMV infection induces endothelial cell dysfunction are poorly understood. Here, we evaluated whether HCMV regulated endothelial cell function and assessed the underlying mechanisms. Microarray analysis in human umbilical vein endothelial cells (HUVECs) treated with HCMV AD169 strain in the presence of hyperglycemia and hyperlipidemia revealed differential expression of genes involved in hypertension. Further analyses validated that the regulator of G-protein signaling 5 (RGS5) gene was downregulated in infected HUVECs and showed that HCMV infection promoted HUVEC proliferation, whereas hyperglycemia and hyperlipidemia inhibited HUVEC proliferation. Additionally, treatment with decitabine (DAC) and RGS5 reversed the effects of HCMV infection on HUVEC proliferation, but not triggered by hyperglycemia and hyperlipidemia. In summary, upregulation of RGS5 may be a promising treatment for preventing HCMV-induced hypertension.

Highlights

Interactions between human cytomegalovirus (HCMV) infection and environmental factors can increase susceptibility to essential hypertension (EH)
Of the 8,579 mRNAs significantly altered in comparison with human umbilical vein endothelial cells (HUVECs) treated by high glucose (HG) and oxidized low-density lipoprotein (ox-LDL) with or without HCMV infection, 2,472 genes www.nature.com/scientificreports
It was indicated that HCMV infection was associated with hypertension in Kazakh and Han Chinese populations, and interactions with environmental factors, e.g. HG and high fat, could increase susceptibility to hypertension[11]

Summary

Introduction

Interactions between human cytomegalovirus (HCMV) infection and environmental factors can increase susceptibility to essential hypertension (EH). Microarray analysis in human umbilical vein endothelial cells (HUVECs) treated with HCMV AD169 strain in the presence of hyperglycemia and hyperlipidemia revealed differential expression of genes involved in hypertension. A number of previous studies revealed that hypertension is associated with genetic and environmental factors, and with human cytomegalovirus (HCMV) infection, DNA methylation, and other epigenetic mechanisms[3]. Studies demonstrated that HCMV can infect endothelial cells (ECs), macrophages and smooth muscle cells, which are all of great importance in the pathogenesis of vascular diseases[12,13]. HCMV infection is related to the pathogenesis of EH since it elicits vascular cells (e.g., ECs) dysfunction.

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Conclusion