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Pediatric pulmonary hypertension: insulin-like growth factor-binding protein 2 is a novel marker associated with
Megan Griffiths1, Jun Yang1, Melanie Nies1
1Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Insights
Insulin-like growth factor binding protein 2 (IGFBP2) is a novel marker for pediatric pulmonary arterial hypertension (PAH), linked to poorer outcomes and survival. IGF axis dysregulation offers new therapeutic targets for this severe childhood disease.
Area of Science:
- Endocrinology
- Cardiovascular Research
- Pediatric Pulmonology
Background:
- Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are implicated in cardiovascular function and pulmonary arterial hypertension (PAH) pathobiology.
- Limited research exists on the specific pathobiology of pediatric PAH.
- The IGF axis may play a role in the development and progression of pediatric PAH.
Purpose of the Study:
- To determine the diagnostic and prognostic value of IGF1 and IGFBP2 in pediatric PAH.
- To investigate the association of IGF1 and IGFBP2 with PAH severity and clinical outcomes in children.
Main Methods:
- Serum samples from pediatric PAH patients (n=175) and asthmatic controls (n=46) were analyzed for IGF1 and IGFBP2 using ELISA.
- Biomarker levels were correlated with demographic data, clinical variables, and PAH severity metrics.
- Cox proportional hazard models were used to assess prognostic value for survival endpoints.
Main Results:
- Serum IGF1 levels were lower, while IGFBP2 levels were higher in pediatric PAH patients compared to controls.
- IGF1 negatively correlated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR).
- IGFBP2 positively correlated with PVR, negatively with cardiac output and 6-minute walk distance, and predicted death, transplant, or shunt (HR 8.8, p<0.001).
Conclusions:
- Elevated circulating IGFBP2 is a novel diagnostic and prognostic marker in pediatric PAH.
- IGFBP2 levels are associated with increased disease severity, functional status, and reduced survival.
- IGF axis dysregulation, particularly increased IGFBP2, highlights potential mechanistic and therapeutic targets for pediatric PAH.
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.
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.
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).
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.
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.
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