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Published on: May 11, 2015
Elevated hypoxia-inducible factor-1α in pediatric patients with patent ductus arteriosus: a pilot study
Oksana Trębacz1,2, Patrycja Florek3, Jacek Podlewski4
1Department of Pediatrics and Pediatric Gastroenterology with Pediatric Cardiology Subdivision, St. Jadwiga the Queen Clinical Regional Hospital, No. 2, ul. Lwowska 60, Rzeszów, 35-301, Poland. oksana.trebacz@if-pan.edu.pl.
Insights
Children with patent ductus arteriosus (PDA) show elevated levels of hypoxia-inducible factor-1α (HIF-1α), even without pulmonary hypertension. This finding suggests HIF-1α may play a role in non-cyanotic congenital heart disease.
Area of Science:
- Cardiology
- Pediatrics
- Molecular Biology
Background:
- Hypoxia-inducible factor-1α (HIF-1α) is crucial for cellular responses to low oxygen and is elevated in complex cyanotic congenital heart disease (CHD) with pulmonary hypertension (PH).
- Circulating HIF-1α levels in non-cyanotic CHD, such as patent ductus arteriosus (PDA), are not well understood.
Purpose of the Study:
- To evaluate serum HIF-1α levels in children with PDA.
- To compare HIF-1α levels in PDA patients with healthy children and those with complex CHD post-Fontan palliation.
Main Methods:
- Eighty children were divided into PDA (n=34), Fontan (n=23), and control (n=23) groups.
- Collected data included complete blood counts, serum HIF-1α levels, and clinical characteristics.
- Multiple regression and ROC curve analyses identified predictors of HIF-1α variability and diagnostic accuracy.
Main Results:
- PDA patients had the highest median HIF-1α levels (0.62 ng/mL) compared to Fontan patients (0.52 ng/mL) and controls (0.48 ng/mL) (p=0.03).
- Hemoglobin, age, and red blood cell count predicted 53.9% of HIF-1α variance in the CHD cohort (p<0.01).
- Hematocrit <36.6% and hemoglobin <12.9 g/dL accurately identified elevated HIF-1α (>1.1 ng/mL).
Conclusions:
- Children with PDA, irrespective of PH, exhibit increased circulating HIF-1α.
- Further investigation is required to determine the clinical significance of HIF-1α in non-cyanotic CHD.
Background:
Children with complex cyanotic congenital heart disease (CHD) and with pulmonary hypertension (PH) commonly experience hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular responses to low oxygen, and its levels are elevated in these conditions. However, HIF-1α concentrations in non-cyanotic CHD, such as patent ductus arteriosus (PDA), remain largely unknown. This study aimed to evaluate circulating serum HIF-1α levels in patients with PDA and compare them with those in healthy children and in patients with complex CHD after Fontan palliation.
Methods:
Eighty children were assigned to three groups: PDA group (n = 34), Fontan group (n = 23), and healthy controls (n = 23). Complete blood counts, serum HIF-1α levels, and baseline clinical characteristics were collected. Multiple regression analysis was performed to identify predictors of HIF-1α variability. Receiver operating characteristic (ROC) curves were analyzed to evaluate the ability of selected variables to predict increased HIF-1α levels.
Results:
Patients with PDA exhibited the highest median [IQR] HIF-1α levels (0.62 [0.41-1.18] ng/mL), compared to patients in the Fontan group (0.52 [0.34-0.73] ng/mL), and healthy controls (0.48 [0.33-0.63] ng/mL) (p = 0.03). In the combined CHD cohort, hemoglobin, age, and red blood cell count formed the best predictive model, explaining 53.9% of HIF-1α variance (p < 0.01). Hematocrit < 36.6% and hemoglobin < 12.9 g/dL showed the best diagnostic accuracy for identifying HIF-1α > 1.1 ng/mL.
Conclusions:
Children with PDA, even without PH, exhibit elevated circulating HIF-1α. Further research is needed to clarify the clinical relevance of HIF-1α in non-cyanotic CHD.
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