Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity release_en5ezap32vgkzis6ddnbazizay

by Melanie K. Nies, Jun Yang, Megan Griffiths, Rachel Damico, Jie Zhu, Dhananjay Vaydia, Zongming Fu, Stephanie Brandal, Eric D. Austin, Dunbar D. Ivy, Paul M. Hassoun, Jennifer E. Van Eyk (+1 others)

Published in Pulmonary Circulation by Wiley.

2022   Volume 12, Issue 2, e12039

Abstract

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.
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Type  article-journal
Stage   published
Date   2022-04-20
Language   en ?
DOI  10.1002/pul2.12039
PubMed  35514776
PMC  PMC9063962
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