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

Keywords

  • Inflammation
  • Pulmonary hypertension
  • Vasodilators

ASJC Scopus subject areas

  • Clinical Biochemistry

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