ArticleSignal transduction and targeted therapy2021
The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- Endothelial Ffar4 protects against diabetic kidney disease by potentiating endogenous retinoic acid metabolism.Cellular & molecular biology letters · 2026Article
- Metabolic Syndrome-Driven Changes in Cardiac Lymphatic Endothelium: mRNA Expression and Emerging Questions.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- ScRNA-seq reveals dynamic macrophage heterogeneity in chronic liver disease progression and prognostic biomarkersFrontiers in immunology · 2026Article
- Transcriptomic profiling of endothelial progenitor cells in post-COVID-19 patients: Insights at 3 and 6-month post-infection.iScience · 2025Article
- Aging affects reprogramming of pulmonary capillary endothelial cells after lung injury in male mice.Nature communications · 2025Article
- Multi-Omics and Clinical Validation Identify Key Glycolysis- and Immune-Related Genes in Sepsis.International journal of general medicine · 2025Article
- Nutritional Advantages of Walnut (Food science & nutrition · 2025Review
- Mechanism of KLF2 in young mice with pneumonia induced by Streptococcus pneumoniae.Journal of cardiothoracic surgery · 2024Article
- Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis.Nature cardiovascular research · 2024Article
- Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.Immunity, inflammation and disease · 2024Review
- COVID-19 Coagulopathy.Life (Basel, Switzerland) · 2024Review
- Transcriptional responses of brain endothelium toMicrobiology spectrum · 2024Article
- A novel mouse model of familial combined hyperlipidemia and atherosclerosis.Acta pharmacologica Sinica · 2024Article
- Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.BMC medical genomics · 2024Article
- Gamma protocadherins in vascular endothelial cells inhibit Klf2/4 to promote atherosclerosis.bioRxiv : the preprint server for biology · 2024Article
- The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.Frontiers in immunology · 2024Article
- Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung.Frontiers in immunology · 2024Article
- Long COVID: Molecular Mechanisms and Detection Techniques.International journal of molecular sciences · 2023Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
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Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
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.
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