scholarly journals Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Line Jee Hartmann Rasmussen ◽  
Jens Emil Vang Petersen ◽  
Jesper Eugen-Olsen
Keyword(s):  
Risk Factors ◽  
Plasminogen Activator ◽  
Chronic Inflammation ◽  
Immune Activation ◽  
Urokinase Plasminogen Activator ◽  
Morbidity And Mortality ◽  
Inflammatory Biomarkers ◽  
Urokinase Plasminogen Activator Receptor ◽  
Age Related ◽  
Plasminogen Activator Receptor

Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade inflammation that plays a major role in immunosenescence and in development and progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, and SCI is typically measured by combining biomarkers of acute inflammation and infection, e.g., CRP, IL-6, and TNFα. In this review, we highlight 10 properties and characteristics that are shared by the blood protein soluble urokinase plasminogen activator receptor (suPAR) and SCI, supporting the argument that suPAR is a biomarker of SCI: (1) Expression and release of suPAR is upregulated by immune activation; (2) uPAR and suPAR exert pro-inflammatory functions; (3) suPAR is associated with the amount of circulating immune cells; (4) Blood suPAR levels correlate with the levels of established inflammatory biomarkers; (5) suPAR is minimally affected by acute changes and short-term influences, in contrast to many currently used markers of systemic inflammation; (6) Like SCI, suPAR is non-specifically associated with multiple diseases; (7) suPAR and SCI both predict morbidity and mortality; (8) suPAR and SCI share the same risk factors; (9) suPAR is associated with risk factors and outcomes of inflammation above and beyond other inflammatory biomarkers; (10) The suPAR level can be reduced by anti-inflammatory interventions and treatment of disease. Assessing SCI has the potential to inform risk for morbidity and mortality. Blood suPAR is a newer biomarker which may, in fact, be a biomarker of SCI since it is stably associated with inflammation and immune activation; shares the same risk factors as many age-related diseases; is both elevated by and predicts age-related diseases. There is strong evidence that suPAR is a prognostic marker of adverse events, morbidity, and mortality. It is associated with immune activity and prognosis across diverse conditions, including kidney disease, cardiovascular disease, cancer, diabetes, and inflammatory disorders. Thus, we think it likely represents a common underlying disease-process shared by many diseases; that is, SCI. We review the supporting literature and propose a research agenda that can help test the hypothesis that suPAR indexes SCI, with the potential of becoming the new gold standard for measuring SCI.

scholarly journals Soluble urokinase plasminogen activator receptor (suPAR) as a prognostic marker of mortality in healthy, general and patient populations: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e036125 ◽  
Author(s):  
Jens Emil Vang Petersen ◽  
Thomas Kallemose ◽  
Karen D Barton ◽  
Avshalom Caspi ◽  
Line Jee Hartmann Rasmussen
Keyword(s):  
Systematic Review ◽  
Plasminogen Activator ◽  
Chronic Inflammation ◽  
Prognostic Marker ◽  
Meta Analysis ◽  
Urokinase Plasminogen Activator ◽  
Urokinase Plasminogen Activator Receptor ◽  
Improve Risk Stratification ◽  
Population Type ◽  
Plasminogen Activator Receptor

IntroductionChronic inflammation is increasingly recognised as a major contributor to disease, disability and ultimately death, but measuring the levels of chronic inflammation remains non-canonised, making it difficult to relate chronic inflammation and mortality. Soluble urokinase plasminogen activator receptor (suPAR), an emerging biomarker of chronic inflammation, has been proposed as a prognostic biomarker associated with future incidence of chronic disease and mortality in general as well as patient populations. Proper prognostic biomarkers are important as they can help improve risk stratification in clinical settings and provide guidance in treatment or lifestyle decisions as well as in the design of randomised trials. Here, we wish to summarise the evidence about the overall association of the biomarker suPAR with mortality in healthy, general and patient populations across diseases.Methods and analysisThe search will be conducted using Medline, Embase and Scopus databases from their inception to 03 June 2020 to identify studies investigating ‘suPAR’ and ‘mortality’. Observational studies and control groups from intervention studies written in English or Danish will be included. The ‘Quality In Prognosis Studies’ tool will be used to assess the risk of bias for the studies included. Unadjusted and adjusted mortality outcome measures (eg, risk ratios, ORs, HRs) with 95% CIs will be extracted for healthy individuals, general and patient populations. The primary outcome is all-cause mortality within any given follow-up. Subgroup analyses will be performed based on time of outcome, cause of death, population type, adjustments for conventional risk factors and inflammation markers.Ethics and disseminationThis systematic review will synthesise evidence on the use of suPAR as a prognostic marker for mortality. The results will be disseminated by publication in a peer-reviewed journal. Data used will be obtained from published studies, and ethics approval is therefore not necessary for this systematic review.Trial registration number PROSPEROCRD42020167401.

Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Blacks

2021 ◽  
Author(s):  
Nels C. Olson ◽  
Laura M. Raffield ◽  
Anne H. Moxley ◽  
Tyne W. Miller-Fleming ◽  
Paul L. Auer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Genetic Variation ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Urokinase Plasminogen Activator Receptor ◽  
Enhancer Element ◽  
Plasminogen Activator Receptor

Background: suPAR (Soluble urokinase plasminogen activator receptor) has emerged as an important biomarker of coagulation, inflammation, and cardiovascular disease (CVD) risk. The contribution of suPAR to CVD risk and its genetic influence in the Black population have not been evaluated. Methods: We measured suPAR in 3492 Blacks from the prospective, community-based JHS (Jackson Heart Study). Cross-sectional associations of suPAR with lifestyle and CVD risk factors were assessed, whole-genome sequence data were used to evaluate genetic associations of suPAR, and relationships of suPAR with incident CVD outcomes and overall mortality were estimated over follow-up. Results: In Cox models adjusted for traditional CVD risk factors, estimated glomerular filtration rate, and CRP (C-reactive protein), each 1-SD higher suPAR was associated with a 21% to 31% increased risk of incident coronary heart disease, heart failure, stroke, and mortality. In the genome-wide association study, 2 missense (rs399145 encoding p.Thr86Ala, rs4760 encoding p.Phe272Leu) and 2 noncoding regulatory variants (rs73935023 within an enhancer element and rs4251805 within the promoter) of PLAUR on chromosome 19 were each independently associated with suPAR and together explained 14% of suPAR phenotypic variation. The allele frequencies of each of the four suPAR-associated genetic variants differ considerably across African and European populations. We further show that PLAUR rs73935023 can alter transcriptional activity in vitro. We did not find any association between genetically determined suPAR and CVD in JHS or a larger electronic medical record-based analyses of Blacks or Whites. Conclusions: Our results demonstrate the importance of ancestry-differentiated genetic variation on suPAR levels and indicate suPAR is a CVD biomarker in Black adults.

scholarly journals Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Therese Torgersen Bigseth ◽  
John Abel Engh ◽  
Jens Egeland ◽  
Eivind Andersen ◽  
Ole Andreas Andreassen ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Plasminogen Activator ◽  
Immune Activation ◽  
Urokinase Plasminogen Activator ◽  
Low Grade ◽  
Urokinase Plasminogen Activator Receptor ◽  
Identification Test ◽  
Disorder Identification ◽  
Plasminogen Activator Receptor ◽  
Low Grade Inflammation

Abstract Background There is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent. Method In this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables. Results Adjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p < 0.001). The association between suPAR and CDSS score was significant in females (p < 0.001) but not in males. Immune activation measured by hsCRP was not associated with depressive symptoms after adjusting for BMI. Conclusion Our findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms.

scholarly journals Soluble urokinase plasminogen activator receptor is linearly associated with dietary quality and predicts mortality

2019 ◽  
Vol 121 (6) ◽  
pp. 699-708 ◽  
Author(s):  
Peter B. S. Törnkvist ◽  
Thomas H. Haupt ◽  
Line J. H. Rasmussen ◽  
Steen Ladelund ◽  
Ulla Toft ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Chronic Inflammation ◽  
Dietary Habits ◽  
Urokinase Plasminogen Activator ◽  
Dietary Quality ◽  
Inverse Association ◽  
Regression Analyses ◽  
Urokinase Plasminogen Activator Receptor ◽  
Risk Of Death ◽  
Plasminogen Activator Receptor

AbstractChronic inflammation is associated with disease risk and mortality in the general population. Soluble urokinase plasminogen activator receptor (suPAR) is a stable marker of chronic inflammation, and a higher serum-concentration of suPAR is found in individuals with an unhealthy lifestyle such as smoking. This article investigates the association between suPAR and dietary quality measured with the dietary quality score (DQS). The DQS is an index of the overall quality of an individual’s dietary habits assessed through a self-administered FFQ. Furthermore, this article investigates the association of both suPAR and the DQS with CVD risk and mortality in the general Danish population. We analysed 5347 individuals aged 30–60 years from the Danish Inter99 study cohort. Multiple linear regression analyses showed a linear inverse association between the DQS and suPAR (P=0·0005). Cox regression analyses showed an 18 (95 % CI 9, 26) % increase in the risk of death from any cause with each 1 ng/ml increase in suPAR. We found no significant association between the DQS and the mortality (hazard ratio: 1·16, 95 % CI 0·79, 1·69). All analyses were adjusted for demographics and lifestyle factors. The association between the DQS and suPAR on the one hand and suPAR and mortality on the other supports the argument that low dietary quality may constitute a health risk through its influence on chronic inflammation. Future research should examine whether suPAR is modifiable through changes in dietary habits.

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