Dataset Information

Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor).

ABSTRACT: Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow-up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45-children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research.

SUBMITTER: Bourassa KJ

PROVIDER: S-EPMC8453112 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor).

Bourassa Kyle J KJ Rasmussen Line J H LJH Danese Andrea A Eugen-Olsen Jesper J Harrington HonaLee H Houts Renate R Poulton Richie R Ramrakha Sandhya S Sugden Karen K Williams Ben B Moffitt Terrie E TE Caspi Avshalom A

Brain, behavior, and immunity 20210702

Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, ...[more]

PMID: 34224821

Similar Datasets

Project description: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.

Project description:BackgroundThe soluble urokinase plasminogen activator receptor (suPAR) is related to hepatic inflammation and fibrosis and has been suggested to participate in the development of liver cirrhosis. Therefore, the aim of the current study was to measure the concentration of suPAR in the hepatic vein of cirrhotic patients during a liver vein catheterization to identify a possible hepatic suPAR generation. Furthermore, we explored if suPAR levels were associated with the degree of cirrhosis and liver dysfunction.Methods and patientsWe included 105 cirrhotic patients and 19 liver-healthy controls. Blood was sampled from the hepatic vein and the femoral artery and suPAR was measured by enzyme-linked immunosorbent assay.ResultsWe identified significantly higher median suPAR concentrations among the cirrhotic patients (7.2 ng/ml in the hepatic vein; 6.8 ng/ml in the femoral artery) compared to the controls (2.6 ng/ml, respectively, p-values <0.001). However, the median hepatic suPAR formation was 0.0 ng/ml in both groups. We observed significantly increasing suPAR levels according to higher Child classes (4.5 ng/ml, 6.9 ng/ml and 9.0 ng/ml, Child A, B, C respectively; p-value<0.001), and significantly higher median suPAR concentrations in patients with ascites versus patients without ascites (8.1 ng/ml versus 5.3 ng/ml, respectively, p-value<0.001). suPAR levels were significantly related to bilirubin (r = 0.48, p<0.001), the hepatic venous pressure gradient (r = 0.39, p<0.001), the cardiac index (r = 0.24, p = 0.02) and the plasma volume (r = 0.33, p = 0.001), whereas suPAR levels were significantly inversely related to albumin (r = -0.59, p<0.001), plasma coagulation factors (r-0.39, p<0.001), the mean arterial pressure (r = -0.28, p = 0.004), the systemic vascular resistance (r = 0.26, p = 0.007), the indocyanine green clearance (r = -0.51, p<0,001) and the galactose elimination capacity (r = -0.39, p<0.001).ConclusionWe identified elevated suPAR concentration in cirrhotic patients, which correlated significantly with the degree of cirrhosis and liver failure, but we were not able to demonstrate hepatic suPAR generation per se. This suggests that further investigations of the source of suPAR in cirrhotic patients need to be undertaken.

Dataset Information

Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor).

Publications

Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets