Related Experiment Video
Updated: Nov 3, 2025
Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells
Koon-Chu Yaiw1,2, Abdul-Aleem Mohammad1,2, Chato Taher1,2
1Department of Medicine, Solna, Microbial Pathogenesis Unit, Karolinska Institutet, SE 171 64 Stockholm, Sweden.
Insights
Human cytomegalovirus (HCMV) infection reduces levels of endothelin-1 (ET-1), a peptide linked to vascular disease. This viral effect on ET-1 production may impact blood vessel tone.
Area of Science:
- Virology
- Cardiovascular Biology
- Molecular Biology
Background:
- Human cytomegalovirus (HCMV) is an opportunistic pathogen linked to atherosclerosis.
- Endothelin-1 (ET-1) is a peptide associated with vasculopathies, often overexpressed in disease states.
Purpose of the Study:
- To investigate the effect of HCMV infection on ET-1 production in endothelial and smooth muscle cells.
- To determine the mechanisms by which HCMV influences ET-1 expression.
Main Methods:
- In vitro infection of human endothelial and smooth muscle cells with HCMV.
- Assessment of ET-1 mRNA and protein levels using quantitative PCR, immunofluorescence, and ELISA.
- Evaluation of endothelin converting enzyme-1 (ECE-1) expression and the role of viral IE2-p86 protein.
Main Results:
- HCMV infection significantly decreased ET-1 mRNA and bioactive ET-1 secretion in both cell types.
- Accumulation of the ET-1 precursor protein was observed in infected endothelial cells.
- HCMV infection inhibited ECE-1 expression, and the viral IE2-p86 protein was identified as a key modulator of ET-1 expression.
- Ganciclovir treatment did not reverse the suppressive effects of HCMV on ET-1.
Conclusions:
- HCMV infection suppresses ET-1 production in vascular cells through mechanisms involving IE2-p86 and inhibition of ECE-1.
- The study reveals a novel interaction between HCMV and the ET-1 pathway, with potential implications for vascular regulation.
- Further in vivo studies are needed to confirm the impact of HCMV-mediated ET-1 reduction on vascular tone.
Abstract:
Human cytomegalovirus (HCMV) is an opportunistic pathogen that has been implicated in the pathogenesis of atherosclerosis. Endothelin-1 (ET-1), a potent vasoconstrictive peptide, is overexpressed and strongly associated with many vasculopathies. The main objective of this study was to investigate whether HCMV could affect ET-1 production. As such, both endothelial and smooth muscle cells, two primary cell types involved in the pathogenesis of atherosclerosis, were infected with HCMV in vitro and ET-1 mRNA and proteins were assessed by quantitative PCR assay, immunofluorescence staining and ELISA. HCMV infection significantly decreased ET-1 mRNA and secreted bioactive ET-1 levels from both cell types and promoted accumulation of the ET-1 precursor protein in infected endothelial cells. This was associated with inhibition of expression of the endothelin converting enzyme-1 (ECE-1), which cleaves the ET-1 precursor protein to mature ET-1. Ganciclovir treatment did not prevent the virus suppressive effects on ET-1 expression. Consistent with this observation we identified that the IE2-p86 protein predominantly modulated ET-1 expression. Whether the pronounced effects of HCMV in reducing ET-1 expression in vitro may lead to consequences for regulation of the vascular tone in vivo remains to be proven.
