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Endoglin (CD105) Up-regulation in Pulmonary Microvasculature of Ventilated Preterm Infants

¹ Department of Pathology, Women and Infants Hospital; and ² Department of Pathology and Laboratory Medicine, Brown Medical School, Providence, Rhode Island

Correspondence and requests for reprints should be addressed to Monique E. De Paepe, M.D., Women and Infants Hospital, Department of Pathology, 101 Dudley Street, Providence, RI 02905. E-mail: mdepaepe{at}wihri.org

Rationale: Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined.

Objectives: Endoglin (CD105), a hypoxia-inducible transforming growth factor-β coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs.

Methods: We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour.

Measurements and Main Results: Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of long-term ventilated infants with BPD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs.

Conclusions: BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.

Key Words: chronic lung disease of prematurity • bronchopulmonary dysplasia • neonatal lung disease • angiogenesis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Microvascular development is disrupted in premature infants with bronchopulmonary dysplasia (BPD), resulting in abnormalities of lung structure that occur during the late canalicular and early saccular stages of lung development. Mechanisms that impair angiogenesis in BPD are incompletely understood. What This Study Adds to the Field This study suggests that endoglin, an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions, contributes to BPD-associated dysangiogenesis.

 

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