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

Michael E. Yeager, Kelley L. Colvin, Allen D Everett, Kurt R. Stenmark, D. Dunbar Ivy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)257-267
Number of pages11
JournalProteomics - Clinical Applications
Volume6
Issue number5-6
DOIs
StatePublished - Jun 2012

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Vasodilator Agents
Proteomics
Plasmas
Hemopexin
Aryldialkylphosphatase
Immunosorbents
Haptoglobins
Proteome
Electrophoresis
Design of experiments
Mass spectrometry
Assays
Therapeutics
Gels
Enzymes
Familial Primary Pulmonary Hypertension
Proteins
Phagocytes
Mass Spectrometry
Research Design

Keywords

  • Inflammation
  • Pulmonary hypertension
  • Vasodilators

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Plasma proteomics of differential outcome to long-term therapy in children with idiopathic pulmonary arterial hypertension. / Yeager, Michael E.; Colvin, Kelley L.; Everett, Allen D; Stenmark, Kurt R.; Ivy, D. Dunbar.

In: Proteomics - Clinical Applications, Vol. 6, No. 5-6, 06.2012, p. 257-267.

Research output: Contribution to journalArticle

Yeager, Michael E. ; Colvin, Kelley L. ; Everett, Allen D ; Stenmark, Kurt R. ; Ivy, D. Dunbar. / Plasma proteomics of differential outcome to long-term therapy in children with idiopathic pulmonary arterial hypertension. In: Proteomics - Clinical Applications. 2012 ; Vol. 6, No. 5-6. pp. 257-267.
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