scholarly journals Association of soluble urokinase plasminogen activator receptor levels with fibrotic and vascular manifestations in systemic sclerosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247256
Author(s):  
Sheraz Butt ◽  
Jørgen L. Jeppesen ◽  
Line Vinderslev Iversen ◽  
Mogens Fenger ◽  
Jesper Eugen-Olsen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Urokinase Plasminogen Activator ◽  
Pulmonary Involvement ◽  
Digital Ulcers ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activator Receptor ◽  
Predicted Values

Objective We assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc). Methods suPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers. Results Overall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22–79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3–10.2 [median: 2.9 (p25–p75: 2.3–3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p <0.0001) and FVC (r = -0.26, p = 0.004), also when adjusted for age, sex, and pulmonary hypertension. A suPAR cut-off level of >2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco <50% or FVC < 60% of the predicted values. Similarly, 19 (90%) had a suPAR >2.5 ng/mL among those diagnosed with pulmonary fibrosis vs. 59 (60%) among those who did not (p = 0.008). suPAR values were not associated with vascular manifestations. Conclusion suPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.

Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis

2015 ◽  
Vol 53 (11) ◽  
Author(s):  
Nóra Legány ◽  
Gergely Toldi ◽  
Jörg H.W. Distler ◽  
Christian Beyer ◽  
Balázs Szalay ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Digital Ulcers ◽  
Matrix Remodeling ◽  
Urokinase Plasminogen Activator Receptor ◽  
Test Parameters ◽  
Organ Specific ◽  
Plasminogen Activator Receptor

AbstractUrokinase plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ-specific involvement.suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling.suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g., Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis.Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity.

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

2017 ◽  
Vol 70 (12) ◽  
pp. 1063-1068
Author(s):  
Gitte Kristensen ◽  
Kasper Drimer Berg ◽  
Solvej Lippert ◽  
Ib Jarle Christensen ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Specific Antigen ◽  
Roc Curves ◽  
Urokinase Plasminogen Activator ◽  
Clinicopathological Parameters ◽  
Prognostic Information ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activator Receptor

AimsLymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed whether plasma levels of the soluble uPAR forms uPAR(I-III), uPAR(II-III) and uPAR(I) were associated with the risk of N1 disease in men with clinically localised PCa.MethodsThe present study includes all men (n=518) who underwent radical prostatectomy (RP) for clinically localised PCa, 29 of whom had N1 disease. Soluble uPAR forms were measured using three time-resolved fluorescence immunoassays. The prognostic value of the different uPAR forms together with clinicopathological parameters for N1 disease were analysed using logistic regression, receiver operating characteristic (ROC) regression analysis and quantified using the areas under the ROC curve (AUC).ResultsAll soluble uPAR levels were significantly (p=0.03) higher in patients with N1 disease compared with patients with N0/x disease. ROC curves including clinical tumour stage, biopsy Gleason score, prostate-specific antigen and percent positive biopsies had an AUC of 87.7% for prediction of N1 disease. With the addition of uPAR(I) to the model, the AUC increased to 88.4%.ConclusionsAddition of uPAR(I) level to known diagnostic parameters did not increase the prediction of N1 disease following RP in men with clinically localised PCa. Our results indicate that the plasma levels at diagnosis of the different uPAR forms do not hold important predictive or prognostic information in men with clinically localised PCa.

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