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

Department of Pediatric Critical Care, University of Colorado Denver, Denver, CO 80045, USA.
PROTEOMICS - CLINICAL APPLICATIONS (Impact Factor: 2.68). 06/2012; 6(5-6):257-67. DOI: 10.1002/prca.201100078
Source: PubMed

ABSTRACT 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.
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.
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.
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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Available from: David Dunbar Ivy, Aug 25, 2015
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    • "Second, this study supports the idea that iron plays a role in the development of PH, perhaps through increased iron-mediated protein carbonylation. Finally, we sought to investigate the plasma proteome of children with PH as a basis to predict outcome in response to vasodilator therapy[90]. Interestingly, we found correlations between serum amyloid A and serum amyloid P to outcome. "
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