Tue Jun 16 2020

Urokinase plasminogen as activator receptor

Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein found in the bloodstream. Increasing scientific evidence supports the efficacy of suPAR as a diagnostic and predictive biomarker for several diseases. Use of suPAR in clinical practice can assist in risk assessment and early diagnosis of crucial diseases. This can enable prompt treatment and good prognosis in patients. This article will discuss briefly the scientific background of suPAR and its’ use in clinical practice.

What is urokinase-type plasminogen activator (uPA)?

Urokinase-type plasminogen activator (uPA) is a serine protease, meaning it is an enzyme with an amino acid (serine) in its’ molecular structure. Serine proteases are found abundantly in different living organisms. In human beings, serine proteases are involved in major biological functions such as inflammatory processes and immune response. In the human body, uPA is known to perform important functions of tissue repair and remodelling1.

What is urokinase-type plasminogen activator (uPA)?

Urokinase-type plasminogen activator (uPA) is a serine protease, meaning it is an enzyme with an amino acid (serine) in its’ molecular structure. Serine proteases are found abundantly in different living organisms. In human beings, serine proteases are involved in major biological functions such as inflammatory processes and immune response. In the human body, uPA is known to perform important functions of tissue repair and remodelling1.

What is soluble urokinase-type plasminogen activator (suPAR)?

The protein suPAR is found in the bloodstream of all individuals. Unlike its precursor form uPAR which is bound to the cell membrane, suPAR circulates in the blood and can be easily measured. Most importantly, the level of suPAR reflects the extent of inflammation and immune activation in the body. Thus, it can be used as an effective biomarker for risk assessment, as well as, for diagnostic evaluation of various diseases4.Schematic representation of uPA receptor. The GPI-anchor links uPAR to the cell membrane making it available for uPA to bind to the receptor (1 A). When the receptor is cleaved between the GPI-anchor and D3, it becomes soluble (suPAR) (1 B). suPAR is a stable protein that can be measured in various body fluids. uPAR: uPA receptor, suPAR: soluble uPAR, 1: Domain 1, D2: Domain 2, D3: Domain
The level of suPAR in the bloodstream reflects the extent of a disease. Hence, suPAR levels can be used to assess the severity of the disease and prognosis of the patient. In general, a low suPAR level is suggestive of good health and a high suPAR level indicates presence of an underlying disease. As a marker of immune activation, suPAR bears resemblance to the inflammatory biomarker C-reactive protein (CRP). However, suPAR is a stronger indicator of disease severity and progression than CRP. For instance, many acute medical patients have low CRP but high suPAR and have a high risk of severe disease and mortality4

What is suPAR used for?

The result of the suPAR analysis provides information about the presence or absence of a disease. At the same time, higher than normal suPAR levels reflect the seriousness of a disease. This is particularly useful when a patient displays specific signs and symptoms of a disease and the suPAR analysis reveals elevated concentrations of the biomarker. This can help diagnose a specific disease and rule out other conditions. On the other hand, when suPAR levels are low (below 3 ng/ml) the patient is at a low risk and has a good prognosis5. This may aid in the decision to discharge or admit the acute medical patient seeking the emergency department, and more and more hospitals are including suPAR as a routine risk assessment marker in the hospital6.

What is the level of suPAR?

In healthy blood donors, the suPAR level is usually between 1-3 ng. In acute medical patients it is higher, but most patients are below 3 ng/ml. In critically ill patients, the suPAR level is often above 10 ng/ml (7,8).

When is suPAR high?

High suPAR level is associated with multiple-morbid conditions and disease progression. One in eight patients have a suPAR level above 6 ng/ml, and such high suPAR is associated with lengthy hospital stay, readmission, and mortality. If suPAR is even higher (>10 ng/ml), there is increased risk of liver and kidney failure6,7,8.

What is the purpose of suPAR in the clinical practice?

suPAR contributes to the overall evaluation of the patients’ burden of disease. Patients with a high suPAR level need immediate clinical attention, while a low level of suPAR indicates low risk in patients. suPAR levels are elevated in inflammatory conditions, cancerous diseases, cardiovascular diseases, acute kidney injury, sepsis, etc6.

1. Crippa MP. Urokinase-type plasminogen activator. International Journal of Biochemical and Cell Biology. 2007.
2. Mahmood N, Mihalcioiu C, Rabbani SA. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): Diagnostic, prognostic, and therapeutic applications. Frontiers in Oncology. 2018.
3. Noh H, Hong S, Huang S. Role of urokinase receptor in tumor progression and development. Theranostics. 2013. 3 (7): 487-495.
4. Eugen-Olsen, J. et al. Circulating soluble urokinase plasminogen activator receptorpredicts cancer, cardiovascular disease, diabetes and mortality in the generalpopulation. J. Intern. Med. 2010;268, 296–308.
5. Eapen DJ, Manocha P, Ghasemzedah N, et al. Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events. Journal of the American Heart Association 2014;3: e001118.
6. Rasmussen LJH et al. Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study. Crit Care Med. 2018 Dec;46(12):1961-1968.
7. The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS), Melis Şirinoğlu et al, 2016, Journal of Infection and Chemotherapy 23
8. Risbro R, Christensen IJ, Hogdall C, Brunner N, Hogdall E. Soluble urokinase plasminogen activator receptor measurements: influence of sample handling. Int J Biol Markers 2001;16: 233–9.

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