Vascular changes after intra-amniotic endotoxin in preterm lamb lungs

Area of Science:

• Neonatal Physiology
• Pulmonary Medicine
• Developmental Biology

Background:

• Chorioamnionitis is linked to preterm birth and bronchopulmonary dysplasia (BPD), a condition marked by abnormal lung development and vascular issues.
• Understanding the vascular impact of chorioamnionitis is crucial for preventing BPD in premature infants.

Purpose of the Study:

• To investigate the vascular effects of intra-amniotic endotoxin exposure, mimicking chorioamnionitis, in a preterm lamb model.
• To evaluate changes in endothelial protein expression and pulmonary vascular remodeling following antenatal inflammation.

Main Methods:

• Preterm lambs received intra-amniotic endotoxin or saline, followed by delivery at 122 days gestational age.
• Assessed bronchoalveolar lavage fluid protein, VEGF mRNA, and key endothelial protein expression (VEGF, VEGFR-2, eNOS, PECAM-1, Tie-2).
• Examined pulmonary artery vascular remodeling, including medial smooth muscle and adventitial collagen deposition.

Main Results:

• Intra-amniotic endotoxin increased lung vascular permeability and decreased VEGF 165 mRNA.
• Coordinated decrease in VEGF, VEGFR-2, eNOS, PECAM-1, and Tie-2 protein expression observed in lung tissue.
• Selective reduction in eNOS in small pulmonary vessels and evidence of medial smooth muscle hypertrophy and adventitial fibrosis were noted.

Conclusions:

• Antenatal inflammation in preterm lambs inhibits endothelial cell protein expression.
• This inhibition is followed by vascular remodeling in small pulmonary arteries.
• Exposure to antenatal inflammation may be a significant factor in the vascular development abnormalities leading to BPD.