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

Lesley Baerts,Inger Brandt,Marc Vanderheyden,Pieter Van Der Veken,Yannick Waumans,Wolfgang Jungraithmayr,Ingrid De Meester,Meijing Wang

doi:10.1371/journal.pone.0141408

Lesley Baerts, Inger Brandt + Show 6 more

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https://doi.org/10.1371/journal.pone.0141408

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Abstract

BackgroundThe 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.MethodologyWe 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 DPP4 activity and SDF1α levels in patients with varying degrees of heart failure.ResultsThe immunoreactivities of SDF1α and its degradation products were determined with three immunoassays. A one hour incubation of SDF1α 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, SDF1α 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 SDF1α levelsConclusionsWe propose that all samples for SDF1α analysis should be collected in the presence of at least a DPP4 inhibitor. In doing so, we found higher SDF1α levels in subgroups of patients with heart failure. Our work supports the need for further research on the clinical relevance of SDF1α levels in cardiac disease.

Highlights

In recent years, the chemokine Stromal cell-Derived Factor 1α (SDF1α or CXCL12) has been shown to play a role in cardiovascular diseases [1] and to be a promising biomarker [2,3]
dipeptidyl peptidase 4 (DPP4) activity in serum was not altered in the heart failure population
CXCR4, SDF1α is involved in the homing of progenitor/stem cells thereby favoring the repair of injured myocardium through angiogenesis [1,4,5,6]

Summary

Introduction

The chemokine Stromal cell-Derived Factor 1α (SDF1α or CXCL12) has been shown to play a role in cardiovascular diseases [1] and to be a promising biomarker [2,3]. Trimming by DPP4 results in the formation of SDF1α3–68 which lacks chemotactic properties but is a powerful antagonist of the CXCR4 [9,10] In this regard, Broxmeyer et al showed that DPP4 inhibition significantly increases homing and engraftment of hematopoietic stem cells [11]. Other enzymes that might play a role in N-terminal cleavage are leukocyte elastase, matrix metalloproteases 1, 2, 3, 9, 13 and 14, and cathepsin G generating SDF1α4–68, SDF1α5–68 and SDF1α6–68 respectively As mentioned, these cleavage products lack biological activity [12,13,14]. The correct interpretation of SDF1α levels is complicated by the occurrence of truncated forms that possess an altered biological activity

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