Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19

Kundura, Lucy; Gimenez, Sandrine; Cezar, Renaud; André, Sónia; Younas, Mehwish; Lin, Yea-Lih; Portalès, Pierre; Lozano, Claire; Boulle, Charlotte; Reynes, Jacques; Thierry, Vincent; Mettling, Clément; Pasero, Philippe; Muller, Laurent; Lefrant, Jean‐Yves; Roger, Claire; Claret, Pierre‐Géraud; Duvnjak, Sandra; Loubet, Paul; Sotto, Albert; Tran, Tú-Anh; Estaquier, Jérǒme; Corbeau, Pierre

doi:10.1016/j.jaci.2022.06.020

Cited by 13 publications

(10 citation statements)

References 41 publications

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“…Moreover, they also observed the presence of DNA damage in up to 50% of their PBMCs and T-cell apoptosis. At the same time, ICU patients exhibit more T-cell apoptosis and lymphopenia than non-ICU patients 22 . Alexandra Ioana Moatar reported that differentially expressed microRNA are primarily enriched in mitotic cell cycle in the heart, lung, and kidney 23 .…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, these cytotoxic lymphocytes have been involved in the downregulation of immune activation via their ability to kill T cells, NK cells, and antigen-presenting cells 34 . The reduced level of CD8 + T cells and NK cells could impair negative feedback on immune activation in several COVID-19 patients 22 .In one report, T cells unique to speci c SARS-CoV-2 peptides were enriched in patients with severe disease, raising the intriguing possibility that the immunological response to speci c epitopes may contribute to disease severity 35 .…”

Section: Discussionmentioning

confidence: 99%

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Identification of key genes related to immune cells in patients with COVID-19 via Integrated Bioinformatics-Based Analysis

Chen

2023

Preprint

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Background COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis. Methods The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms. Results There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signalling pathway. As much as 358 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signalling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI: 0.920–0.988), 0.941(95% CI: 0.892 − 0.980), and 0.929(95% CI: 0.880 − 0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells. Conclusions Our study discovered that CDC25A, PDCD6 and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Identification of key genes related to immune cells in patients with COVID-19 via Integrated Bioinformatics-Based Analysis

Chen

2023

Preprint

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“…The state of hyperstimulation of the immune system that occurs in severely ill patients contributes to autoimmune manifestations and is associated with an increased need for oxygen therapy ( Gagiannis et al, 2020 ). Moreover, it was recently reported that Ang II induces ROS release from monocytes able to induce DNA damages and apoptosis in neighboring T-cells leading to lymphopenia in certain patients with severe forms of COVID-19 ( Kundura et al, 2022 ). It is neither the purpose of this paragraph to discuss the complex pattern of immune response in COVID-19 (e.g., a decrease in the total number of CD4+ and CD8+ T cells, B cells, and NK and a recruitment of neutrophils; a massive increase in the release of inflammatory cytokines or ‘cytokine storm’, and chemokines such as IL-2, IL6, IL-7, IL-8, IL-10, TNF, IFN; Amor et al, 2020 ; Campbell and Kahwash, 2020 ; Han et al, 2020 ; Luo et al, 2020 ; Mehta et al, 2020 ; Tay et al, 2020 ; Vitte et al, 2020 ; Zheng et al, 2020 ), nor is it to review the abnormal expression of Ag II in COVID-19 patients that could stimulate proinflammatory processes ( Naftilan and Oparil, 1978 ; Moore et al, 2015 ; Varanat et al, 2017 ; Silva et al, 2020 ; Raghavan et al, 2021 ; Vandestienne et al, 2021 ; Yamamoto et al, 2021 ), but rather to briefly summarize the contribution of anti-ACE2 and anti-AT1R auto-antibodies in COVID-19, since these molecules could play an important role in the immunological puzzle of clinical variability of the disease.…”

Section: Immune Response Against Sars-cov-2 and Auto-antibodies Again...mentioning

confidence: 99%

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Devaux

Camoin-Jau

2022

Front. Microbiol.

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It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled “ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome”), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients’ therapy.

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“…The latest research showed a novel pathogenic mechanism, the overexpression of T-cell surface Fas and DNA damage attributed to AngII-driven ROS generation by the monocytes in some COVID-19 patients, leading to peripheral mononuclear blood cell apoptosis ( Kundura et al, 2022 ). It is worth noting that intensive care unit (ICU) patients present more T-cell apoptosis and lymphopenia than non-ICU; nevertheless, the plasma level of AngII and monocytic ROS production are lower.…”

Section: Lung-protective Mechanisms Of Plant Polysaccharidesmentioning

confidence: 99%

Plant polysaccharides with anti-lung injury effects as a potential therapeutic strategy for COVID-19

Huang

Zhang²,

Duan³

et al. 2022

Front. Pharmacol.

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When coronavirus disease 2019 (COVID-19) develops into the severe phase, lung injury, acute respiratory distress syndrome, and/or respiratory failure could develop within a few days. As a result of pulmonary tissue injury, pathomorphological changes usually present endothelial dysfunction, inflammatory cell infiltration of the lung interstitium, defective gas exchange, and wall leakage. Consequently, COVID-19 may progress to tremendous lung injury, ongoing lung failure, and death. Exploring the treatment drugs has important implications. Recently, the application of traditional Chinese medicine had better performance in reducing fatalities, relieving symptoms, and curtailing hospitalization. Through constant research and study, plant polysaccharides may emerge as a crucial resource against lung injury with high potency and low side effects. However, the absence of a comprehensive understanding of lung-protective mechanisms impedes further investigation of polysaccharides. In the present article, a comprehensive review of research into plant polysaccharides in the past 5 years was performed. In total, 30 types of polysaccharides from 19 kinds of plants have shown lung-protective effects through the pathological processes of inflammation, oxidative stress, apoptosis, autophagy, epithelial–mesenchymal transition, and immunomodulation by mediating mucin and aquaporins, macrophage, endoplasmic reticulum stress, neutrophil, TGF-β1 pathways, Nrf2 pathway, and other mechanisms. Moreover, the deficiencies of the current studies and the future research direction are also tentatively discussed. This research provides a comprehensive perspective for better understanding the mechanism and development of polysaccharides against lung injury for the treatment of COVID-19.

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Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19

Cited by 13 publications

References 41 publications

Identification of key genes related to immune cells in patients with COVID-19 via Integrated Bioinformatics-Based Analysis

Identification of key genes related to immune cells in patients with COVID-19 via Integrated Bioinformatics-Based Analysis

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Plant polysaccharides with anti-lung injury effects as a potential therapeutic strategy for COVID-19

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