Serial changes of serum endostatin and angiopoietin-1 levels in preterm infants with severe bronchopulmonary dysplasia and subsequent pulmonary artery hypertension

摘要

Background: In bronchopulmonary dysplasia (BPD), disrupted angiogenesis may result from an imbalance between pro-and anti-angiogenic factors triggered by inflammation, leading to the late development of pulmonary artery hypertension (PAH). Objectives: To investigate whether the levels of serum endostatin (as an anti-angiogenic factor) and angiopoietin-1 (AP-1; as a pro-angiogenic factor) in early life are associated with the development of PAH in preterm infants with severe BPD. Methods: In this prospective cohort study, the levels of serum endostatin and AP-1 were measured from 56 infants (gestational age <30 weeks or birth weight <1,250 g) including severe BPD with PAH ('PAH'; 15 infants) or without PAH ('non-PAH'; 22 infants) and no/mild BPD (19 infants) groups on days 1, 7, 14, and 28 of life. Results: The PAH group consistently underwent more aggressive respiratory management than the non-PAH group, over 1 month after birth. The endostatin level and the ratio of endostatin to AP-1 on day 7 of life were significantly higher in the PAH group than in the non-PAH group or no/mild BPD groups (median 146.6 vs. 102.4/108.0 ng/ml; 62.1 vs. 18.6/14.9). The ratio of endostatin to AP-1 on day 1 was also significantly higher in the PAH group than in the no/mild BPD group (median 31.8 vs. 11.3). Conclusions: An increased serum endostatin to AP-1 ratio may reflect impaired angiogenesis that may preclude the development of PAH.