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The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction
- Source :
- Signal Transduction and Targeted Therapy, Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-9 (2021)
- Publication Year :
- 2021
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
QH301-705.5
Angiogenesis
Atorvastatin
Kruppel-Like Transcription Factors
Cardiology
Vascular Cell Adhesion Molecule-1
Vasodilation
030204 cardiovascular system & hematology
Pharmacology
Article
03 medical and health sciences
0302 clinical medicine
Target identification
Genetics
medicine
Human Umbilical Vein Endothelial Cells
Humans
Biology (General)
Endothelial dysfunction
Gene knockdown
Vascular disease
business.industry
SARS-CoV-2
COVID-19
medicine.disease
Intercellular Adhesion Molecule-1
Cytokine release syndrome
030104 developmental biology
Gene Expression Regulation
KLF2
Medicine
Cytokines
business
medicine.drug
Subjects
Details
- ISSN :
- 20593635
- Volume :
- 6
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Signal transduction and targeted therapy
- Accession number :
- edsair.doi.dedup.....06dedc349daa13ad443cc39fbe3419dd