Endoglin (CD105) up-regulation in pulmonary microvasculature of ventilated preterm infants.
BACKGROUND
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.


OBJECTIVE
Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta 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.


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.
De Paepe
Monique E
ME
Women and Infants Hospital, Department of Pathology, 101 Dudley Street, Providence, RI 02905, USA. mdepaepe@wihri.org
Patel
Chintan
C
Tsai
Amy
A
Gundavarapu
Sravanthi
S
Mao
Quanfu
Q
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000002:abnormalities / Q000098:blood supply*; D008297:Male; D016555:Matched-Pair Analysis; D008833:Microcirculation / Q000254:growth & development / Q000378:metabolism; D018919:Neovascularization, Physiologic; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042683:Angiopoietin-1; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor