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The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction2.59 MB
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Journal article
The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction
Signal Transduction and Targeted Therapy, Vol.6(1), pp.1-9
2021
Appears in COVID-19 Research
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.
Details
- Title
- The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction
- Authors
- Suowen Xu (Author) - University of Science and Technology of ChinaYujie Liu (Author) - University of Science and Technology of ChinaYu Ding (Author) - University of Science and Technology of ChinaSihui Luo (Author) - University of Science and Technology of ChinaXueying Zheng (Author) - University of Science and Technology of ChinaXiumei Wu (Author) - Sun Yat-sen UniversityZhenghong Liu (Author) - University of Science and Technology of ChinaIqra Ilyas (Author) - University of Science and Technology of ChinaSuyu Chen (Author) - University of Science and Technology of ChinaShuxin Han (Author) - University of Science and Technology of ChinaPeter J Little (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - LegacyMukesh K Jain (Author) - Case Western Reserve UniversityJianping Weng (Author) - University of Science and Technology of China
- Publication details
- Signal Transduction and Targeted Therapy, Vol.6(1), pp.1-9
- Publisher
- Nature Publishing Group
- Date published
- 2021
- DOI
- 10.1038/s41392-021-00690-5
- ISSN
- 2059-3635; 2095-9907
- Copyright note
- Copyright (C) 2021 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99572408902621
- Output Type
- Journal article
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