Dataset Information

Circulating Stromal Cell-Derived Factor 1? Levels in Heart Failure: A Matter of Proper Sampling.

ABSTRACT: The chemokine Stromal cell-derived factor 1? (SDF1?, CXCL12) is currently under investigation as a biomarker for various cardiac diseases. The correct interpretation of SDF1? levels is complicated by the occurrence of truncated forms that possess an altered biological activity.We studied the immunoreactivities of SDF1? forms and evaluated the effect of adding a DPP4 inhibitor in sampling tubes on measured SDF1? levels. Using optimized sampling, we measured DPP4 activity and SDF1? levels in patients with varying degrees of heart failure.The immunoreactivities of SDF1? and its degradation products were determined with three immunoassays. A one hour incubation of SDF1? with DPP4 at 37°C resulted in 2/3 loss of immunoreactivity in each of the assays. Incubation with serum gave a similar result. Using appropriate sampling, SDF1? levels were found to be significantly higher in those heart failure patients with a severe loss of left ventricular function. DPP4 activity in serum was not altered in the heart failure population. However, the DPP4 activity was found to be significantly decreased in patients with high SDF1? levels.We propose that all samples for SDF1? analysis should be collected in the presence of at least a DPP4 inhibitor. In doing so, we found higher SDF1? levels in subgroups of patients with heart failure. Our work supports the need for further research on the clinical relevance of SDF1? levels in cardiac disease.

SUBMITTER: Baerts L

PROVIDER: S-EPMC4636157 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Circulating Stromal Cell-Derived Factor 1α Levels in Heart Failure: A Matter of Proper Sampling.

Baerts Lesley L Waumans Yannick Y Brandt Inger I Jungraithmayr Wolfgang W Van der Veken Pieter P Vanderheyden Marc M De Meester Ingrid I

PloS one 20151106 11

<h4>Background</h4>The chemokine Stromal cell-derived factor 1α (SDF1α, CXCL12) is currently under investigation as a biomarker for various cardiac diseases. The correct interpretation of SDF1α levels is complicated by the occurrence of truncated forms that possess an altered biological activity.<h4>Methodology</h4>We studied the immunoreactivities of SDF1α forms and evaluated the effect of adding a DPP4 inhibitor in sampling tubes on measured SDF1α levels. Using optimized sampling, we measured ...[more]

PMID: 26544044

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Project description:AimsThere are limited data examining the role of immune checkpoint (IC) ligands in the pathophysiology of heart failure (HF). Therefore, we explore this in three HF animal models and in three different human cohorts (healthy, stable, and worsening HF).Methods and resultsTranscriptomic analyses of cardiac tissue of three different HF mouse models revealed differentially expressed IC receptors and their ligands compared with control mice. Based on this observation, serum levels of three well-known IC ligands (i.e. sPD-L1, sPD-L2 and galectin-9) were measured in stable HF patients from the Vitamin D Chronic Heart Failure (VitD-CHF) study (n = 101), as well as healthy individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (n = 58). sPD-L1, sPD-L2, and galectin-9 were all associated with New York Heart Association classification. In multivariate linear regression analyses, all three IC ligands were associated with galectin-3 (β = 0.230, β = 0.283, and β = 0.304, respectively). sPD-L1 and galectin-9 were also associated with hs-troponin-T (β = 0.386 and β = 0.314). Regarding prognosis, higher serum levels of sPD-L1 and galectin-9 were significantly associated with increased risk for HF hospitalization and all-cause mortality [hazard ratio 1.69 (1.09-2.59) and hazard ratio 1.50 (1.06-2.12)]. Furthermore, the importance of IC ligands was tested in another stage of HF, namely worsening HF patients. In the worsening HF cohort (The BIOlogy Study to Tailored Treatment in Chronic Heart Failure) (n = 2032), sPD-L2 and galectin-9 were associated with New York Heart Association classification and significantly predicted outcome with an increased relative risk of 15% and 20%, after multivariable adjustment, respectively.ConclusionsIC ligands are expressed in cardiac disease models, and serum levels of IC ligands are elevated in HF patients, are associated with disease severity, and significantly predict prognosis. These data indicate a potential role for IC ligands in HF pathogenesis.

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Dataset Information

Circulating Stromal Cell-Derived Factor 1? Levels in Heart Failure: A Matter of Proper Sampling.

Publications

Circulating Stromal Cell-Derived Factor 1α Levels in Heart Failure: A Matter of Proper Sampling.

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