Roles of hypoxia-inducible factor-1α and its target genes in neonatal hypoxic pulmonary hypertension.

OBJECTIVE

To investigate the role of hypoxia-inducible factor-1α and its target genes in hypoxic pulmonary hypertension in neonates.

PATIENTS AND METHODS

A total of 117 newborns were selected and divided into two groups for clinical experiments: 85 cases in the hypoxic pulmonary hypertension (HPH) group, including mild, moderate and severe subgroups, and 32 cases in the case-control group. ELISA was used to detect the serum HIF-1α, endothelin-1 (ET-1) and adrenomedullin (ADM) levels, and echocardiography was used to detect the dynamic changes in pulmonary artery systolic pressure (PASP), right ventricular ejection fraction (RVEF), tricuspid E peak and A peak ratio (E/A) and right ventricular Tei index.

RESULTS

The average PASP level of the HPH group was significantly higher than that of the control group at 1 d and 3 d after birth (p < 0.05). The average PASP level was still higher in the severe HPH group than that in the control group at 7 d after birth, while the average levels in the mild and moderate HPH groups recovered to the normal. Compared with those in control group, RVEF and E/A of the tricuspid valve were decreased significantly in severe HPH patients (p < 0.05). The Tei indexes of the right ventricle were significantly higher in the mild, moderate and severe HPH groups than those in control group and the right ventricular Tei index was positively correlated with PASP. The levels of serum ADM, HHH-1α and ET-1 in all the three HPH subgroups were significantly higher than those in the control group at 1 d after birth and showed positive correlations with PASP (p < 0.05), except that serum ADM in mild HPH showed no obvious difference from the control group. The levels of serum HIF-1α and ADM in the severe HPH group and the ET-1 levels in the moderate and severe groups were increased significantly at 3 d after birth (p < 0.05).

CONCLUSIONS

The PASP level in neonates with HPH is related to the serum HIF-1α, ET-1 and ADM levels, indicating that hypoxia can increase the level of HIF-1α, which in turn will enhance the expression of downstream target genes ET-1 and ADM, further leading to pulmonary hypertension. The right ventricular Tei index can be used to sensitively detect right ventricular dysfunction of mild, moderate and severe HPH groups.