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Plasma proteomics of differential outcome to long‐term therapy in children with idiopathic pulmonary arterial hypertension
Author(s) -
Yeager Michael E.,
Colvin Kelley L.,
Everett Allen D.,
Stenmark Kurt R.,
Ivy D. Dunbar
Publication year - 2012
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201100078
Subject(s) - medicine , haptoglobin , context (archaeology) , paraoxonase , gastroenterology , cardiology , endocrinology , oxidative stress , biology , paleontology
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 .