The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity

Yatsenko, Tetiana; Skrypnyk, Maksym; Troyanovska, O.O.; Tobita, Morikuni; Osada, Taro; Takahashi, Satoshi; Hattori, Koichi; Heissig, Beate

doi:10.3390/cells12030445

Cited by 9 publications

(2 citation statements)

References 141 publications

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“…The plasminogen-plasmin system, best known for removing fibrin-containing blood clots, controls extracellular matrix degradation and inflammation, the latter due to its ability to activate other proteases and release pro-inflammatory cytokines (13,14). Only a small portion of circulating plasminogen is converted to plasmin.…”

Section: Introductionmentioning

confidence: 99%

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19

Yatsenko,

Rios,

Nogueira

et al. 2024

Front. Immunol.

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Patients with coronavirus disease-2019 (COVID-19) have an increased risk of thrombosis and acute respiratory distress syndrome (ARDS). Thrombosis is often attributed to increases in plasminogen activator inhibitor-1 (PAI-1) and a shut-down of fibrinolysis (blood clot dissolution). Decreased urokinase-type plasminogen activator (uPA), a protease necessary for cell-associated plasmin generation, and increased tissue-type plasminogen activator (tPA) and PAI-1 levels have been reported in COVID-19 patients. Because these factors can occur in free and complexed forms with differences in their biological functions, we examined the predictive impact of uPA, tPA, and PAI-1 in their free forms and complexes as a biomarker for COVID-19 severity and the development of ARDS. In this retrospective study of 69 Japanese adults hospitalized with COVID-19 and 20 healthy donors, we found elevated free, non-complexed PAI-1 antigen, low circulating uPA, and uPA/PAI-1 but not tPA/PAI-1 complex levels to be associated with COVID-19 severity and ARDS development. This biomarker profile was typical for patients in the complicated phase. Lack of PAI-1 activity in circulation despite free, non-complexed PAI-1 protein and plasmin/α2anti-plasmin complex correlated with suPAR and sVCAM levels, markers indicating endothelial dysfunction. Furthermore, uPA/PAI-1 complex levels positively correlated with TNFα, a cytokine reported to trigger inflammatory cell death and tissue damage. Those levels also positively correlated with lymphopenia and the pro-inflammatory factors interleukin1β (IL1β), IL6, and C-reactive protein, markers associated with the anti-viral inflammatory response. These findings argue for using uPA and uPA/PAI-1 as novel biomarkers to detect patients at risk of developing severe COVID-19, including ARDS.

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Section: Introductionmentioning

confidence: 99%

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19

Yatsenko,

Rios,

Nogueira

et al. 2024

Front. Immunol.

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“…tPA can activate plasminogen to mediate the formation of plasmin to facilitate thrombolysis. It has also been shown to play a critical role in facilitating cell migration within the extracellular matrix, while acting as a critical mediator of cellular signalling pathways 26,27,30 . Judicious administration of tPA may bolster the recovery of patients with Acute Respiratory Distress Syndrome, subsequently diminishing mortality associated with COVID-19 28,29 .The causal relationship between hospitalised COVID-19 and tPA highlights the increased risk of thrombotic events that these patients may face.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study

Li,

Zeng,

et al. 2024

Thromb Haemost

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Background: COVID-19 and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers. Methods: We used Two-sample Mendelian Randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using Inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. We used R language for the analysis. Results: All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (OR=0.639, 95%CI: 0.435-0.938) and IL-1R1 (OR=0.603, 95%CI=0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 (MCFD2) and increased C-C motif chemokine 3 (CCL3). Hospitalised COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had lower mean platelet volume (MPV) and platelet count. These changes in TFPI, tPA, IL-1R1, MPV and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis. Conclusions: This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level, mainly by reducing TFPI and IL-1R1. Three other biomarkers also implied that COVID-19 increases thrombosis risk. We confirmed the reduction of platelet count and MPV, providing clues to the pathogenesis of COVID-19 and thrombosis. Our findings may have implications for the prevention and treatment of thrombotic complications in COVID-19 patients.

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Immunologic burden links periodontitis to acute coronary syndrome: levels of CD4 + and CD8 + T cells in gingival granulation tissue

Kayar,

Çelik,

Gözlü

et al. 2024

Clin Oral Invest

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Objective To investigate the proportional variation of macrophage and T-lymphocytes subpopulations in acute coronary syndrome (ACS) patients, its association with periodontitis (P), and to compare with control individuals. Subjects and methods Three groups of subjects participated: one group consisted of 17 ACS patients with P (ACS + P), another group consisted of 22 no ACS + P patients, and a control group consisted of 23 participants with gingivitis (no ACS + G). Macrophage, CD4 + , and CD8 + T-lymphocytes and CD4 + /CD8 + ratio values in gingival tissue were determined histometrically. Results Significant differences were found among three groups regarding the mean number of macrophage (no ACS + P > ACS + P > no ACS + G; p < 0.05) and CD8 + T-lymphocytes (no ACS + P > ACS + P > no ACS + G; p < 0.05). Significant variations were observed between the groups both CD4 + T-lymphocytes densities (ACS + P > no ACS + P and ACS + P > no ACS + G; p < 0.05) and CD4 + / CD8 + ratio (no ACS + P < no ACS + G and ACS + P < no ACS + G; p < 0.05). Conclusions The increased number of CD8 + T-lymphocytes in both group ACS + P and group no ACS + P resulted in a reduction of the CD4 + /CD8 + ratio in gingival tissue when compared with no ACS + G group. Clinical relevance The decrease of CD4 + /CD8 + ratio in gingival tissue reflects periodontitis and may be associated with severe adverse outcomes in people with ACS.

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The Role of the Plasminogen/Plasmin System in Inflammation of the Oral Cavity

Cited by 9 publications

References 141 publications

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study

Immunologic burden links periodontitis to acute coronary syndrome: levels of CD4 + and CD8 + T cells in gingival granulation tissue

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