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Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells.
Nikitopoulou, Ioanna; Fanidis, Dionysios; Ntatsoulis, Konstantinos; Moulos, Panagiotis; Mpekoulis, George; Evangelidou, Maria; Vassiliou, Alice G; Dimakopoulou, Vasiliki; Jahaj, Edison; Tsipilis, Stamatios; Orfanos, Stylianos E; Dimopoulou, Ioanna; Angelakis, Emmanouil; Akinosoglou, Karolina; Vassilaki, Niki; Tzouvelekis, Argyrios; Kotanidou, Anastasia; Aidinis, Vassilis.
  • Nikitopoulou I; GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Fanidis D; Institute of Bio-Innovation, Biomedical Sciences Research Center Alexander Fleming, 16672 Athens, Greece.
  • Ntatsoulis K; Institute of Bio-Innovation, Biomedical Sciences Research Center Alexander Fleming, 16672 Athens, Greece.
  • Moulos P; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, 16672 Athens, Greece.
  • Mpekoulis G; Molecular Virology Laboratory, Department of Diagnostics, Hellenic Pasteur Institute, 11521 Athens, Greece.
  • Evangelidou M; Department of Diagnostics, Hellenic Pasteur Institute, 11521 Athens, Greece.
  • Vassiliou AG; GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Dimakopoulou V; Department of Respiratory Medicine, University Hospital of Patras, 26504 Patras, Greece.
  • Jahaj E; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Tsipilis S; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Orfanos SE; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Dimopoulou I; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Angelakis E; Department of Diagnostics, Hellenic Pasteur Institute, 11521 Athens, Greece.
  • Akinosoglou K; Department of Respiratory Medicine, University Hospital of Patras, 26504 Patras, Greece.
  • Vassilaki N; Molecular Virology Laboratory, Department of Diagnostics, Hellenic Pasteur Institute, 11521 Athens, Greece.
  • Tzouvelekis A; Department of Respiratory Medicine, University Hospital of Patras, 26504 Patras, Greece.
  • Kotanidou A; GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
  • Aidinis V; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos General Hospital, 10676 Athens, Greece.
Int J Mol Sci ; 22(18)2021 Sep 16.
Article in English | MEDLINE | ID: covidwho-1409704
Preprint
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ABSTRACT
Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphodiesterase Inhibitors / Dendritic Cells / Phosphoric Diester Hydrolases / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: Ijms221810006

Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphodiesterase Inhibitors / Dendritic Cells / Phosphoric Diester Hydrolases / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: Ijms221810006