Microvascular significance of TGF-ß axis activation in COVID-19.
Front Cardiovasc Med
; 9: 1054690, 2022.
Article
em En
| MEDLINE
| ID: mdl-36684608
ABSTRACT
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-ß1) 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-ß1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-ß 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-ß 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-ß and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-ß inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Cardiovasc Med
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos