Epidermal growth factor in the lungs of infants developing chronic lung disease

Currie, Andrew; Vyas, Julian; Macdonald, J; Field, David; Kotecha, Sailesh

doi:10.1183/09031936.01.00088201

Cited by 26 publications

(31 citation statements)

References 24 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, Lassus and coworkers (19) described lower VEGF in tracheal aspirates of preterm infants with severe respiratory distress/ BPD compared with control subjects. In contrast, studies by Ambalavanan and Novak (20), D'Angio and coworkers (21), and Currie and coworkers (22) found no correlation between levels of VEGF in tracheal aspirates of preterm infants and risk for development of BPD.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 40%

“…Orchestration of these complex functions is regulated by various pro-and antiangiogenic growth factors, angiogenic chemokines/cytokines, matrix-degrading proteases, and cell-extracellular matrix interactions (47)(48)(49)(50). Previous studies of the molecular regulation of angiogenesis in BPD lungs have focused mainly on the major angiogenic growth factors traditionally associated with vascular morphogenesis, such as VEGF and Ang-1 (9,12,(19)(20)(21)(22). In view of the important role of the accessory TGF-b receptor endoglin (CD105) in a variety of neoplastic and nonneoplastic angiogenic conditions (23)(24)(25)(26)(27)(28)(29)(30), we speculated that endoglin may be implicated in ventilationinduced angiogenesis in preterm lungs as well.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Paepe¹,

Patel²,

Tsai³

et al. 2008

Am J Respir Crit Care Med

View full text Add to dashboard Cite

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-b 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 longterm 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.Keywords: chronic lung disease of prematurity; bronchopulmonary dysplasia; neonatal lung disease; angiogenesis Preterm newborns who require mechanical ventilation and supplemental oxygen are at risk for bronchopulmonary dysplasia (BPD), a chronic lung disease of newborn infants associated with significant mortality and morbidity (1). BPD in the postsurfactant era is seen mainly in very low birthweight infants and affects 30% of infants born between 24 and 28 weeks of gestation, many of whom will require long-term respiratory support (2, 3).The dominant pathological finding in postsurfactant BPD is an arrest in alveolar development, resulting in large and simplified airspaces that show varying degrees of interstitial fibrosis (2,(4)(5)(6)(7)(8). Studies have shown that, in addition to impaired alveolar development, there is also a disruption of pulmonary microvascular development in infants with BPD (8-10) or in BPD-like animal models such as chronically ventilated premature baboons (11,12). In view of the intimate relation between alveolar and microvascular development during pulmonary morphogenesis (13-16), disruption of microvascular development in premature lungs has been implicated as a critical factor in the arrest of alveolar development that i...

show abstract

Section: What This Study Adds To the Fieldmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 99%

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

Paepe¹,

Patel²,

Tsai³

et al. 2008

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Similarly, Lassus and coworkers (27) described lower VEGF in tracheal aspirates of preterm infants with severe respiratory distress/BPD compared with control subjects. In contrast, studies by Ambalavanan and Novak (28), D'Angio and coworkers (29), and Currie and coworkers (30) found no correlation between levels of VEGF in tracheal aspirates of preterm infants and risk for development of BPD.…”

Section: Discussionmentioning

confidence: 58%

Growth of Pulmonary Microvasculature in Ventilated Preterm Infants

Paepe

Mao

Powell

et al. 2006

Am J Respir Crit Care Med

189

158

View full text Add to dashboard Cite

Rationale: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. Objective: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. Methods: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. Measurements: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. Main Results: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. Conclusions:The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.Keywords: bronchopulmonary dysplasia; chronic lung disease of prematurity; neonatal lung disease Despite major advances in perinatal medicine, including the introduction of surfactant therapy, antenatal glucocorticoids, and new ventilator strategies, preterm newborns treated with ventilation and supplemental oxygen frequently develop bronchopulmonary dysplasia (BPD), a chronic lung disease of newborn infants associated with significant mortality and morbidity (1). BPD in the postsurfactant era is seen primarily in very low birth weight infants and affects 30% of infants born at 24 to 28 wk, many of whom will require long-term ventilation and/or supplemental oxygen (2, 3).The dominant pathologic finding at autopsy in postsurfactant BPD is an arrest in alveolar development, resulting in lungs with large and simplified airspaces showing varying degrees of interstitial fibrosis (2, 4-8). Impairment of alveolar formation in BPD leads to long-term global reduction in alveolar number and gas-exchange surface area (6, 7). The ...

show abstract

“…Infants with any evidence of infection, which included prolonged rupture of membranes, an increase in peripheral blood neutrophils, a left shift of neutrophils, systemic infection, an increase in CRP, or positive blood or endotracheal cultures, were excluded from the study. BAL was obtained as previously described (15,16). Briefly, with the infant lying supine and head turned to the left, an FG5 catheter was inserted into the right lower lobe of the infant and two aliquots of 1 mL/kg of saline were instilled and, after two to four ventilator breaths, aspirated back.…”

Section: Methodsmentioning

confidence: 99%

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

et al. 2004

View full text Add to dashboard Cite

Previously, we have reported marked pulmonary inflammation in infants who develop chronic lung disease of prematurity. We revisited these infants who did not have clinical or laboratory evidence of infection and searched for Ureaplasma urealyticum, group B streptococci, and other microbes by reverse transcription-PCR performed on RNA extracted from 93 bronchoalveolar lavage samples. From infants ventilated for respiratory distress syndrome, 6 (gestation, 28 wk; birthweight, 880 g) were positive for U. urealyticum and 11 (25 wk, 800 g) were negative. Five (83%) positive and four (36%) negative infants developed chronic lung disease. Each infant was colonized with either biovar 1 or biovar 2 but not both. U. urealyticum was very weakly detectable in two infants on d 1 but was detected in five of six infants at d 10. Furthermore, pulmonary neutrophils, alveolar macrophages, soluble intercellular adhesion molecule-1, and IL-1␤ on d 10 and IL-6 and IL-8 at d 1 were significantly increased in the positive group. A variety of organisms were identified in six samples between 14 and 21 d of age, but all samples were negative for group B streptococci. Our data suggest that U. urealyticum colonization is associated with the development of pulmonary inflammation in infants who subsequently develop chronic lung disease. CLD remains a common respiratory disorder of preterm infants. Despite significant advances with therapeutic modalities, including the introduction of surfactant, various modes of mechanical ventilation and regular use of antenatal corticosteroids, morbidity and mortality remain high. Many risk factors have been identified and these include mechanical ventilation, oxygen therapy, patent ductus arteriosus, and nosocomial infection. An area that has recently received much attention is antenatal infection (1, 2). Even before the infant is delivered, an inflammatory response has been noted and this inflammation appears to be associated with the development of respiratory disease in the newborn infant (3, 4). One candidate for initiating this inflammation is the mycoplasma Ureaplasma urealyticum (5, 6). This organism has been isolated from the lungs of infants who have developed CLD, but whether U. urealyticum causes acute lung injury in preterm infants or whether the association is with the degree of prematurity remains controversial (7). One approach to confirming or refuting this association is to study the link between the pulmonary inflammatory response, which has now been regularly reported in infants who develop CLD (8 -11), and the presence of U. urealyticum in the lungs of infants who develop CLD.Our previous data have demonstrated that proinflammatory cytokines IL-1 and IL-6, the potent neutrophil chemoattractant IL-8, and soluble adhesion molecule ICAM-1, as well as inflammatory cells, namely neutrophils, are increased in the lungs of infants who subsequently develop CLD (8, 9). These findings have been confirmed by many others (10, 11), and it is now generally accepted that pulmonary inflammation is a r...

show abstract

Epidermal growth factor in the lungs of infants developing chronic lung disease

Cited by 26 publications

References 24 publications

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

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

Growth of Pulmonary Microvasculature in Ventilated Preterm Infants

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

Contact Info

Product

Resources

About