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Intrinsic BMP Antagonist Gremlin-1 as a Novel Circulating Marker in Pulmonary Arterial Hypertension

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Abstract

Gremlin-1, an intrinsic antagonist of bone morphogenetic protein (BMP) signaling, has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, it is unknown whether gremlin-1 can be detected in the circulation of PAH patients and whether it is associated with patients’ functional status and outcome. With a mean level of 242 ± 24 ng/ml, gremlin-1 levels of 31 PAH patients were significantly elevated compared to 151 ± 18 ng/ml in 15 age- and gender-matched healthy subject (p = 0.016). In PAH patients, increasing gremlin-1 levels correlated with N-terminal prohormone of brain natriuretic peptide levels (r = 0.608, p < 0.001) and inversely with the 6-minute walking distance (r = −0.412, p = 0.029). Furthermore, gremlin-1 significantly stratified survival in PAH patients (p = 0.015). Gremlin-1 may represent a new biomarker for PAH which can be linked directly to the underlying pathomechanism. Elevated levels of gremlin-1 are associated with patients’ functional status and survival, thus gremlin-1 neutralization could represent a potential therapeutic strategy to increase BMPR2 signaling.

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Acknowledgments

Medical Faculty of the University of Hamburg (FFM program).

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    Authors and Affiliations

    1. Department of Hematology, Oncology and Stem Cell Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      Jasmin Wellbrock, Lars Harbaum, Hauke Stamm, Jan K. Hennigs, Björn Schulz, Hans Klose, Carsten Bokemeyer & Walter Fiedler

    2. Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Hamburg, Germany

      Nicole Lüneburg

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    1. Jasmin Wellbrock
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    2. Lars Harbaum
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    7. Carsten Bokemeyer
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    Correspondence to Jasmin Wellbrock.

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    Jasmin Wellbrock and Lars Harbaum contributed equally.

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    Wellbrock, J., Harbaum, L., Stamm, H. et al. Intrinsic BMP Antagonist Gremlin-1 as a Novel Circulating Marker in Pulmonary Arterial Hypertension. Lung 193, 567–570 (2015). https://doi.org/10.1007/s00408-015-9735-5

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    • DOI: https://doi.org/10.1007/s00408-015-9735-5

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