Microvascular significance of TGF-β axis activation in COVID-19
As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusua...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.1054690/full |
| _version_ | 1797959872619216896 |
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| author | Lauren M. Arguinchona Caterina Zagona-Prizio Megan E. Joyce Edward D. Chan Edward D. Chan Edward D. Chan James P. Maloney |
| author_facet | Lauren M. Arguinchona Caterina Zagona-Prizio Megan E. Joyce Edward D. Chan Edward D. Chan Edward D. Chan James P. Maloney |
| author_sort | Lauren M. Arguinchona |
| collection | DOAJ |
| description | As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs. Notably, anticoagulation improves outcomes in some COVID-19 patients. The protein transforming growth factor-beta (TGF-β1) has constitutive roles in maintaining a healthy microvasculature through its roles in regulating inflammation, clotting, and wound healing. However, after infection (including viral infection) TGF-β1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-β signaling in immune cells and its localization in areas of microvascular injury are now well-described in COVID-19, and such events may contribute to the acute respiratory distress syndrome and skin micro-thrombosis outcomes frequently seen in severe COVID-19. The high concentration of TGF-β in platelets and in other cells within microvascular thrombi, its ability to activate the clotting cascade and dysregulate immune pathways, and its pro-fibrotic properties all contribute to a unique milieu in the COVID-19 microvasculature. This unique environment allows for propagation of microvascular clotting and immune dysregulation. In this review we summarize the physiological functions of TGF-β and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-β inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation. |
| first_indexed | 2024-04-11T00:37:46Z |
| format | Article |
| id | doaj.art-1ef6e966b48348108c5d192e720434c4 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-11T00:37:46Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-1ef6e966b48348108c5d192e720434c42023-01-06T13:27:02ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-01-01910.3389/fcvm.2022.10546901054690Microvascular significance of TGF-β axis activation in COVID-19Lauren M. Arguinchona0Caterina Zagona-Prizio1Megan E. Joyce2Edward D. Chan3Edward D. Chan4Edward D. Chan5James P. Maloney6School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesRocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, United StatesNational Jewish Health, Denver, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesAs 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs. Notably, anticoagulation improves outcomes in some COVID-19 patients. The protein transforming growth factor-beta (TGF-β1) has constitutive roles in maintaining a healthy microvasculature through its roles in regulating inflammation, clotting, and wound healing. However, after infection (including viral infection) TGF-β1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-β signaling in immune cells and its localization in areas of microvascular injury are now well-described in COVID-19, and such events may contribute to the acute respiratory distress syndrome and skin micro-thrombosis outcomes frequently seen in severe COVID-19. The high concentration of TGF-β in platelets and in other cells within microvascular thrombi, its ability to activate the clotting cascade and dysregulate immune pathways, and its pro-fibrotic properties all contribute to a unique milieu in the COVID-19 microvasculature. This unique environment allows for propagation of microvascular clotting and immune dysregulation. In this review we summarize the physiological functions of TGF-β and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-β inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation.https://www.frontiersin.org/articles/10.3389/fcvm.2022.1054690/fullfibrosis-pulmonary-histopathology-diagnosisSARS-CoV-2acute respiratory disease syndrome (ARDS)thrombosisTGF-β1TSP1/THBS1 |
| spellingShingle | Lauren M. Arguinchona Caterina Zagona-Prizio Megan E. Joyce Edward D. Chan Edward D. Chan Edward D. Chan James P. Maloney Microvascular significance of TGF-β axis activation in COVID-19 Frontiers in Cardiovascular Medicine fibrosis-pulmonary-histopathology-diagnosis SARS-CoV-2 acute respiratory disease syndrome (ARDS) thrombosis TGF-β1 TSP1/THBS1 |
| title | Microvascular significance of TGF-β axis activation in COVID-19 |
| title_full | Microvascular significance of TGF-β axis activation in COVID-19 |
| title_fullStr | Microvascular significance of TGF-β axis activation in COVID-19 |
| title_full_unstemmed | Microvascular significance of TGF-β axis activation in COVID-19 |
| title_short | Microvascular significance of TGF-β axis activation in COVID-19 |
| title_sort | microvascular significance of tgf β axis activation in covid 19 |
| topic | fibrosis-pulmonary-histopathology-diagnosis SARS-CoV-2 acute respiratory disease syndrome (ARDS) thrombosis TGF-β1 TSP1/THBS1 |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.1054690/full |
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