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Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐base...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063962/ https://www.ncbi.nlm.nih.gov/pubmed/35514776 http://dx.doi.org/10.1002/pul2.12039 |
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author | Nies, Melanie K. Yang, Jun Griffiths, Megan Damico, Rachel Zhu, Jie Vaydia, Dhananjay Fu, Zongming Brandal, Stephanie Austin, Eric D. Ivy, Dunbar D. Hassoun, Paul M. Van Eyk, Jennifer E. Everett, Allen D. |
author_facet | Nies, Melanie K. Yang, Jun Griffiths, Megan Damico, Rachel Zhu, Jie Vaydia, Dhananjay Fu, Zongming Brandal, Stephanie Austin, Eric D. Ivy, Dunbar D. Hassoun, Paul M. Van Eyk, Jennifer E. Everett, Allen D. |
author_sort | Nies, Melanie K. |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐based proteomics analysis to identify circulating biomarkers of PAH. Plasma samples from patients with idiopathic pulmonary arterial hypertension (IPAH, N = 9) and matched normal controls (N = 9) were digested with trypsin and analyzed using data‐dependent acquisition on an Orbitrap mass spectrometer. A total of 826 (false discovery rate [FDR] 0.047) and 461 (FDR 0.087) proteins were identified across all plasma samples obtained from IPAH and control subjects, respectively. Of these, 153 proteins showed >2 folds change (p < 0.05) between groups. Circulating levels of carbonic anhydrase 2 (CA2), plasma kallikrein (KLKB1), and the insulin‐like growth factor binding proteins (IGFBP1‐7) were quantified by immunoassay in an independent verification cohort (N = 36 PAH and N = 35 controls). CA2 and KLKB1 were significantly different in PAH versus control but were not associated with any functional or hemodynamic measurements. Whereas, IGFBP1 and 2 were associated with higher pulmonary vascular resistance, IGFBP2, 4, and 7 with decreased 6‐min walk distance (6MWD), and IGFBP1, 2, 4, and 7 with worse survival. This plasma proteomic discovery analysis suggests the IGF axis may serve as important new biomarkers for PAH and play an important role in PAH pathogenesis. |
format | Online Article Text |
id | pubmed-9063962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90639622022-05-04 Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity Nies, Melanie K. Yang, Jun Griffiths, Megan Damico, Rachel Zhu, Jie Vaydia, Dhananjay Fu, Zongming Brandal, Stephanie Austin, Eric D. Ivy, Dunbar D. Hassoun, Paul M. Van Eyk, Jennifer E. Everett, Allen D. Pulm Circ Research Articles Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐based proteomics analysis to identify circulating biomarkers of PAH. Plasma samples from patients with idiopathic pulmonary arterial hypertension (IPAH, N = 9) and matched normal controls (N = 9) were digested with trypsin and analyzed using data‐dependent acquisition on an Orbitrap mass spectrometer. A total of 826 (false discovery rate [FDR] 0.047) and 461 (FDR 0.087) proteins were identified across all plasma samples obtained from IPAH and control subjects, respectively. Of these, 153 proteins showed >2 folds change (p < 0.05) between groups. Circulating levels of carbonic anhydrase 2 (CA2), plasma kallikrein (KLKB1), and the insulin‐like growth factor binding proteins (IGFBP1‐7) were quantified by immunoassay in an independent verification cohort (N = 36 PAH and N = 35 controls). CA2 and KLKB1 were significantly different in PAH versus control but were not associated with any functional or hemodynamic measurements. Whereas, IGFBP1 and 2 were associated with higher pulmonary vascular resistance, IGFBP2, 4, and 7 with decreased 6‐min walk distance (6MWD), and IGFBP1, 2, 4, and 7 with worse survival. This plasma proteomic discovery analysis suggests the IGF axis may serve as important new biomarkers for PAH and play an important role in PAH pathogenesis. John Wiley and Sons Inc. 2022-04-20 /pmc/articles/PMC9063962/ /pubmed/35514776 http://dx.doi.org/10.1002/pul2.12039 Text en © 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Nies, Melanie K. Yang, Jun Griffiths, Megan Damico, Rachel Zhu, Jie Vaydia, Dhananjay Fu, Zongming Brandal, Stephanie Austin, Eric D. Ivy, Dunbar D. Hassoun, Paul M. Van Eyk, Jennifer E. Everett, Allen D. Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title | Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title_full | Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title_fullStr | Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title_full_unstemmed | Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title_short | Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity |
title_sort | proteomics discovery of pulmonary hypertension biomarkers: insulin‐like growth factor binding proteins are associated with disease severity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063962/ https://www.ncbi.nlm.nih.gov/pubmed/35514776 http://dx.doi.org/10.1002/pul2.12039 |
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