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

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.

• Authors: 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
• Journal: Microorganisms (Microorganisms) Vol. 9 Issue 6 (May 25 2021) ISSN: 2076-2607 [Print] Switzerland
• PMID: 34070407 (Publication Type: Journal Article)