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Pediatric pulmonary hypertension: insulin-like growth factor-binding protein 2 is a novel marker associated with disease severity and survival.

Authors :
Griffiths M
Yang J
Nies M
Vaidya D
Brandal S
Williams M
Matsui EC
Grant T
Damico R
Ivy D
Austin ED
Nichols WC
Pauciulo MW
Lutz K
Rosenzweig EB
Hirsch R
Yung D
Everett AD
Source :
Pediatric research [Pediatr Res] 2020 Dec; Vol. 88 (6), pp. 850-856. Date of Electronic Publication: 2020 Sep 14.
Publication Year :
2020

Abstract

Background: Insulin-like growth factors (IGFs), and their binding proteins (IGFBPs), play a significant role in cardiovascular function and may influence the pathobiology of PAH. We determined the diagnostic and prognostic value of IGF1 and IGFBP2 in pediatric PAH.<br />Methods: Serum was analyzed by ELISA for IGF1 and IGFBP2 in pediatric PAH subjects from the NHLBI PAH Biobank (PAHB, n = 175) and a cohort of asthmatic subjects (n = 46, age 0-21 years) as a chronic pediatric pulmonary disease control. Biomarkers were analyzed with demographic and clinical variables for PAH severity.<br />Results: Serum IGF1 was significantly lower in PAH compared to controls, while IGFBP2 was elevated in PAH subjects compared to controls. In the PAHB, IGF1 was negatively associated with mPAP and PVR, while IGFBP2 was positively associated with PVR and negatively associated with cardiac output and 6-min walk distance. Higher IGFBP2 levels were associated with use of prostacyclin therapy. IGFBP2 was associated with death, transplant, or palliative shunt with a Cox proportional hazard ratio of 8.8 (p < 0.001) but not IGF1 (p = 0.13).<br />Conclusions: Circulating IGFBP2 is a novel marker for pediatric PAH, which is associated with worse functional status, and survival. IGF axis dysregulation may be an important mechanistic target in pediatric pulmonary arterial hypertension.<br />Impact: Pediatric pulmonary hypertension is a severe disease, with poorly understood pathobiology. There are few studies looking at the pathobiology of pulmonary hypertension only in children. The IGF axis is dysregulated in pediatric pulmonary arterial hypertension. IGF axis dysregulation, with increased IGFBP2, is associated with worse clinical outcomes in pediatric pulmonary artery hypertension. IGF axis dysregulation gives new insight into the disease process and may be a mechanistic or therapeutic target.

Details

Language :
English
ISSN :
1530-0447
Volume :
88
Issue :
6
Database :
MEDLINE
Journal :
Pediatric research
Publication Type :
Academic Journal
Accession number :
32927467
Full Text :
https://doi.org/10.1038/s41390-020-01113-x