Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients
Abstract
:1. Introduction
2. Pulmonary Surfactant during SARS-CoV2 Virus Infection
2.1. Etiopathogenesis of PS Damages in COVID-19 Patients
2.2. Molecular Pathway of Surfactant Damage during SARS-CoV-2 Virus Infection
2.3. Surfactant Therapy as a Potential Target in the Treatment of Acute Respiratory Distress Syndrome in COVID-19 Patients
3. Coagulation Processes in Pneumonia Caused by SARS-CoV-2 Infection
3.1. Etiopathogenesis of Clotting Processes in Lungs among COVID-19 Patients
3.2. COVID-19 and an Alternative Way of Activating Platelets
3.3. Molecular Bases of Increased Activity of Von Willebrand Factor during SARS-CoV-2 Infection
3.4. Molecular Abnormalities Cause Hypercoagulability States in Patients with COVID-19
3.5. Molecular Alterations of the Classical and Lectin Complement Pathways Affecting the Process of Hemostasis
3.6. The Coexistence of Coagulation Processes and Changes in the Fibrinolysis Process in the Course of SARS-CoV-2 Infection
4. Pulmonary Fibrosis in the Course of SARS-CoV-2 Virus Infection
4.1. Etiopathogenesis of Pulmonary Fibrosis among COVID-19 Patients
4.2. ACE2-related Profibrotic Pathway Activated by SARS-CoV-2 Infection
4.3. Hyperinflammatory Reaction due to Infection can Induce Pulmonary Fibrosis
4.4. Potential Molecular Markers of Pulmonary Fibrosis in the Course of SARS-CoV-2 Virus Infection
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Surfactant | ||
---|---|---|
Upregulation | Downregulation | SARS-CoV-2 Infection Effects |
- | TTF1 SFTPC SFTPD | Altered immunomodulation Altered air exchange Ineffective alveolar surface tension regulation |
SFTPB | - | Ineffective alveolar surface tension regulation |
GATA6 SFTPA | - | Disrupted immune and anti-inflammation processes |
- | LMCD1 | Disrupted immune and anti-inflammation processes |
SREBP2 | cholesterol biosynthesis genes | Reduction in the phospholipids in the lungs Nonfunctional surfactant proteins Cytokine storm induction |
Coagulation | ||
---|---|---|
Upregulation | Downregulation | SARS-CoV-2 Infection Effects |
Von Willebrand factor, ICAM-1, VCAM-1 | - | Platelets activation Clotting initiation Increased risk of thrombosis |
TIMP1, MMP2, MMP11, VWF | - | Impacted coagulation processes - Platelet adhesion Development of inflammation |
CD62P (P-selectin) TF (tissue factor) | - | Excessive platelet activation Initiation of the extrinsic coagulation cascade Induction of hypercoagulability |
PABPC4, VKORC1 | ADAMTS13 | Induction of hypercoagulability |
TLR3, TLR4, TLR7, TLR8 | - | Induction of hypercoagulability Initiation of the extrinsic coagulation cascade |
MASP1, MASP2 | - | Activation of the classical and lectin complement pathways Catalytic role against prothrombin and fibrinogen |
SERPINE1 | - | Inhibition of the fibrinolysis process |
PLAT PLG FGB | uPA uPAR | Local fibrinolysis reduction and pulmonary thrombosis predisposition D-dimer production |
- | THBD, PROS1 | Development of thrombotic complications |
Fibrosis | ||
---|---|---|
Upregulation | Downregulation | SARS-CoV-2 Infection Effects |
TGF | ACE2/Ang- (1-7)/MasR axis | Inflammation and fibrosis promotion |
Th1 cells, GM, CSF, IL-6, IL-10, IL 1, IL-1, TNF | - | Cytokine storm induction Remodeling of the lung tissue/fibrosis |
KL-6 antigen | - | Pulmonary fibrosis promotion |
MMP9, MMP7 | MMP2 | Pulmonary fibrosis promotion |
YKL-40 | - | Important role in the tissue remodeling |
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Krygier, A.; Szmajda-Krygier, D.; Świechowski, R.; Pietrzak, J.; Wosiak, A.; Wodziński, D.; Balcerczak, E. Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients. Biomolecules 2022, 12, 1845. https://doi.org/10.3390/biom12121845
Krygier A, Szmajda-Krygier D, Świechowski R, Pietrzak J, Wosiak A, Wodziński D, Balcerczak E. Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients. Biomolecules. 2022; 12(12):1845. https://doi.org/10.3390/biom12121845
Chicago/Turabian StyleKrygier, Adrian, Dagmara Szmajda-Krygier, Rafał Świechowski, Jacek Pietrzak, Agnieszka Wosiak, Damian Wodziński, and Ewa Balcerczak. 2022. "Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients" Biomolecules 12, no. 12: 1845. https://doi.org/10.3390/biom12121845