Plasma proteomics of differential outcome to long-term therapy in children with idiopathic pulmonary arterial hypertension

Authors

  • Michael E. Yeager,

    Corresponding author
    1. Department of Bioengineering, University of Colorado Denver, CO, USA
    • Department of Pediatric Critical Care, University of Colorado Denver, CO, USA
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  • Kelley L. Colvin,

    1. Department of Pediatric Critical Care, University of Colorado Denver, CO, USA
    2. Department of Pediatric Cardiology, University of Colorado Denver, CO, USA
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  • Allen D. Everett,

    1. Department of Pediatrics, Pediatric Cardiology, Johns Hopkins University, Baltimore, MD, USA
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  • Kurt R. Stenmark,

    1. Department of Pediatric Critical Care, University of Colorado Denver, CO, USA
    2. Developmental Lung Biology Lab, University of Colorado Denver, CO, USA
    3. Cardiovascular Pulmonary Research, Denver, CO, USA
    4. Gates Center for Regenerative Medicine and Stem Cell Biology, Denver, CO, USA
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  • D. Dunbar Ivy

    1. Department of Pediatric Cardiology, University of Colorado Denver, CO, USA
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  • Colour Online: See the article online to view Fig. 1 in colour.

Correspondence: Dr. Michael E. Yeager, University of Colorado Denver Health Sciences, 12700 E. 19th Avenue, B131 Aurora, CO 80045, USA

E-mail:Michael.yeager@ucdenver.edu

Fax: +1-303 724 4198

Abstract

Purpose

The prognosis for children with IPAH unresponsive to therapy is poor. We investigated the plasma proteome for a molecular basis of good versus poor outcome to long-term vasodilator therapy.

Experimental design

Plasma was collected at baseline or shortly after therapy initiation and following chronic vasodilator therapy, then divided into those with good outcome (n = 8), and those with a poor outcome (n = 7). To identify proteins unique to either outcome, we used differential gel electrophoresis and mass spectrometry. Results were confirmed by commercial enzyme-linked immunosorbent assay.

Results

Before and after therapy, SAA-4 was 4-fold lower in those with good outcome compared to those with poor outcome, while serum paraoxonase/arylesterase-1 was increased 2-fold in those with good outcome versus poor outcome. After therapy, haptoglobin and hemopexin were 1.45- and 1.8-fold lower, respectively, in those with a good versus poor outcome. Among those with a good outcome, SAP was 1.3-fold lower prior to therapy.

Conclusions and clinical relevance

SAP and SAA-4 regulate circulating mononuclear phagocytes. As such, they may contribute to the differential response to chronic vasodilator therapy in the context of inflammation in IPAH.

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