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Updated: Oct 29, 2025
Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction
Suowen Xu1, Yujie Liu2, Yu Ding1
1Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Insights
Loss of kruppel-like factor 2 (KLF2) in endothelial cells contributes to COVID-19 vascular disease. Augmenting KLF2 levels with treatments like atorvastatin may offer therapeutic benefits for COVID-19 patients.
Area of Science:
- Vascular Biology
- Immunology
- Pharmacology
Background:
- Coronavirus disease 2019 (COVID-19) is increasingly recognized as an endothelial disease, characterized by endothelial dysfunction contributing to multi-organ injuries.
- Endothelial dysfunction is a key factor in COVID-19 pathogenesis and its cardiovascular complications.
- Kruppel-like factor 2 (KLF2) is a critical regulator of vascular homeostasis, making it a potential therapeutic target.
Purpose of the Study:
- To investigate whether KLF2 can serve as a therapeutic target for COVID-19-induced endothelial dysfunction.
- To evaluate the role of KLF2 in endothelial inflammation and monocyte adhesion in the context of COVID-19.
Main Methods:
- Endothelial cells were treated with serum from COVID-19 patients.
- Gene expression of KLF2, ICAM1, and VCAM1 was analyzed.
- Cytokine effects (IL-1β, TNF-α) on KLF2 expression were assessed.
- Pharmacologic (atorvastatin, tannic acid) and genetic approaches were used to modulate KLF2 levels.
- Next-generation RNA sequencing was performed on atorvastatin-treated cells.
- KLF2 knockdown was utilized to assess its role in mediating atorvastatin's effects.
Main Results:
- COVID-19 patient serum reduced KLF2 expression and increased monocyte adhesion in endothelial cells, associated with elevated ICAM1 and VCAM1.
- Pro-inflammatory cytokines IL-1β and TNF-α decreased KLF2 gene expression.
- Augmenting KLF2 levels via atorvastatin, tannic acid, or genetic overexpression attenuated COVID-19 serum-induced endothelial inflammation and monocyte adhesion.
- Atorvastatin treatment induced a cardiovascular protective transcriptome, enhancing vasodilation, anti-inflammation, antioxidant status, anti-thrombosis, anti-fibrosis, and reducing angiogenesis.
- Knockdown of KLF2 partially reversed the protective effects of atorvastatin.
Conclusions:
- Reduced KLF2 expression is implicated in the vascular disease associated with COVID-19.
- Therapeutic strategies aimed at increasing KLF2 levels show promise for ameliorating COVID-19-induced endothelial dysfunction and vascular complications.
Abstract:
Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its patho-mechanism being incompletely understood. Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. The objective of the present study is to evaluate whether kruppel-like factor 2 (KLF2), a master regulator of vascular homeostasis, represents a therapeutic target for COVID-19-induced endothelial dysfunction. Here, we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1β and TNF-α, two cytokines elevated in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Pharmacologic (atorvastatin and tannic acid) and genetic (adenoviral overexpression) approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis, and reduced angiogenesis). Finally, knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion. Collectively, the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.
