The Science of suPAR
suPAR is a clinically validated biomarker discovered in Denmark that has been extensively researched for over 20 years and utilized in more than 1,000,000 tests.
The broad support from research across diverse populations confirms suPAR's reliability as a tool for predicting critical health outcomes, including mortality and chronic disease risk.
The suPAR Protein
Originally identified as a receptor for uPA, which activates plasmin from plasminogen, uPAR also interacts with various proteins and supports vital cellular functions such as migration, adhesion, angiogenesis, proliferation, and chemotaxis. It is primarily found on the surface of immune cells including neutrophils, activated T-cells, macrophages, endothelial cells, and smooth muscle cells.
suPAR is the soluble form of uPAR. As illustrated in Figure 1, uPAR is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. The binding of uPA to uPAR facilitates the cleavage of this anchor, resulting in the shedding of the receptor. Once the GPI anchor is cleaved, uPAR detaches from the membrane and circulates in the bloodstream as suPAR, contributing to various immune and inflammatory responses.
The History of suPAR
Discovered in 1991 as a cancer progression marker, suPAR is linked to numerous chronic diseases, including cardiovascular, hepatic, renal, and pulmonary conditions. Elevated suPAR levels correlate with poorer outcomes in various infectious diseases like tuberculosis, HIV, malaria, sepsis, meningitis, and pneumonia, and in critically ill patients.
Due to its association with chronic inflammation, suPAR has been rigorously investigated as a predictive marker for chronic diseases and cancer in the broader population.
The Role of suPAR in Immunity and Patient Prognosis
The crystal structure of suPAR was elucidated in April 2006 and published in the journal Science, demonstrating that its three-domain structure can rotate around its central axis to engage multiple complex ligands. This structural flexibility enables suPAR to maintain a versatile binding pocket, crucial for its involvement in a wide array of biological activities.
Expressed primarily on the surfaces of immune cells like monocytes and activated T-cells, uPAR participates in several key immune mechanisms such as migration, adhesion, angiogenesis, fibrinolysis, and proliferation. When uPAR is shed from these cells, it becomes soluble uPAR (suPAR).
uPAR aids the invasion of either neoplastic or inflammatory cells by concentrating urokinase-driven proteolysis at the cell interface. When released in pathological conditions, suPAR triggers cellular receptors, thereby promoting chemotaxis and enhancing the immune response.
Studies indicate that there are no genetic variations that cause inherently high levels of suPAR in humans. This implies that elevated suPAR levels are generally the result of an immune activation or a response to specific health challenges. Furthermore, elevated suPAR levels are consistently linked with poor disease outcomes, regardless of the infection type.
Supported by over 1,000 peer-reviewed studies, suPAR is a leading global prognostic biomarker across various diseases
What’s a Healthy suPAR Level? Insights from Blood Donors
Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants. Haastrup E, et al. PLOS One, 2014.
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Diet and suPAR: How Healthy Eating Improves Your Biomarker Levels
Soluble Urokinase Plasminogen Activator Receptor is Linearly Associated with Dietary Quality and Predicts Mortality. Törnkvist PBS, et al. British Journal of Nutrition, 2019.
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suPAR: Your Early Warning System for Chronic Inflammation
Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation. Rasmussen LJH, Petersen JEV, Eugen-Olsen J. Frontiers in Immunology, 2021.
suPAR and Longevity: Predicting Health and Disease
Circulating Soluble Urokinase Plasminogen Activator Receptor Predicts Cancer, Cardiovascular Disease, Diabetes, and Mortality. Eugen-Olsen J, et al. Journal of Internal Medicine, 2010.
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suPAR: A Predictor for Cardiovascular Health
Soluble Urokinase Plasminogen Activator Receptor: A Risk Factor for Carotid Plaque, Stroke, and Coronary Artery Disease. Persson M, et al. Stroke, 2014.
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Accelerated Aging: suPAR’s Role in Biological Age
Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging. Rasmussen LJH, et al. Journal of Gerontology, 2021.
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suPAR: A Causal Factor in Kidney Disease
Soluble Urokinase Receptor and Chronic Kidney Disease. Hayek SS, et al. New England Journal of Medicine, 2015.
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Soluble Urokinase Receptor and Acute Kidney Injury
Hayek SS, et al. New England Journal of Medicine, 2020.
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Stressful Life Events and Chronic Inflammation
Linking Stressful Life Events and Chronic Inflammation Using suPAR. Bourassa KJ, et al. Brain, Behavior, and Immunity, 2021.
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Education and Health: suPAR Explains the Link
suPAR Mediates the Effect of a Lower Education Level on Adverse Outcomes in Patients with Coronary Artery Disease.Füller D, et al. European Journal of Preventive Cardiology, 2024.
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The Connection Between Loneliness and Elevated suPAR
Social Isolation, Loneliness, and Inflammation: A Multi-Cohort Investigation. Matthews T, et al. Brain, Behavior, and Immunity, 2023.
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