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 language | English (US) |
|---|---|
| Pages (from-to) | 257-267 |
| Number of pages | 11 |
| Journal | Proteomics - Clinical Applications |
| Volume | 6 |
| Issue number | 5-6 |
| DOIs | |
| State | Published - Jun 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Plasma proteomics of differential outcome to long-term therapy in children with idiopathic pulmonary arterial hypertension
AU - Yeager, Michael E.
AU - Colvin, Kelley L.
AU - Everett, Allen D
AU - Stenmark, Kurt R.
AU - Ivy, D. Dunbar
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Inflammation
KW - Pulmonary hypertension
KW - Vasodilators
UR - http://www.scopus.com/inward/record.url?scp=84863212767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863212767&partnerID=8YFLogxK
U2 - 10.1002/prca.201100078
DO - 10.1002/prca.201100078
M3 - Article
C2 - 22653875
AN - SCOPUS:84863212767
VL - 6
SP - 257
EP - 267
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
SN - 1862-8346
IS - 5-6
ER -