Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells

Koon-Chu Yaiw; Abdul-Aleem Mohammad; Chato Taher; Huanhuan Leah Cui; Helena Costa; Ourania N Kostopoulou; Masany Jung; Alice Assinger; Vanessa Wilhelmi; Jiangning Yang; Klas Strååt; Afsar Rahbar; John Pernow; Cecilia Söderberg-Nauclér

doi:10.3390/microorganisms9061137

Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells

Microorganisms. 2021 May 25;9(6):1137. doi: 10.3390/microorganisms9061137.

Authors

Koon-Chu Yaiw^{1

2}, Abdul-Aleem Mohammad^{1

2}, Chato Taher^{1

2}, Huanhuan Leah Cui^{1

2}, Helena Costa^{1

2}, Ourania N Kostopoulou³, Masany Jung^{1

2}, Alice Assinger⁴, Vanessa Wilhelmi^{1

2}, Jiangning Yang⁵, Klas Strååt⁶, Afsar Rahbar^{1

2}, John Pernow⁵, Cecilia Söderberg-Nauclér^{1

2}

Affiliations

¹ Department of Medicine, Solna, Microbial Pathogenesis Unit, Karolinska Institutet, SE 171 64 Stockholm, Sweden.
² Division of Neurology, Karolinska University Hospital, SE 171 64 Stockholm, Sweden.
³ Department of Oncology and Pathology, Karolinska Institutet, SE 171 64 Stockholm, Sweden.
⁴ Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria.
⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet and University Hospital Solna, SE 171 64 Stockholm, Sweden.
⁶ Department of Medicine, Division of Hematology, BioClinicum and Centre for Molecular Medicine, Karolinska University, Hospital Solna and Karolinska Institutet, SE 171 64 Stockholm, Sweden.

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.

Keywords: endothelial cells; endothelin-1; human cytomegalovirus; immediate-early; smooth muscle cells.

Abstract

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