Endostatin Concentration in Cord Plasma Predicts the Development of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

Janér, Joakim; Andersson, Sture; Kajantie, Eero; Lassus, Patrik

doi:10.1542/peds.2008-1339

Cited by 36 publications

(25 citation statements)

References 28 publications

(24 reference statements)

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“…19 Among pediatric diseases associated with PH, biomarkers in BPD remain the most extensively studied. 20,21 For example, angiogenic (VEGF, PIGF, endostatin, ANG-1), 22–27 inflammatory (IL-1b, IL-6, IL-8, IL-10, IL-17, interferon-γ, RANTES, and TNF-β), 28–31 and epithelial and fibrotic markers (MMP9, TIMP1) 32,33 have been identified as possible predictors of disease risk or severity in BPD. However, these markers have not been clearly correlated to development of BPD-associated PVD and rarely studied in validation cohorts.…”

Section: Proteomic Strategies For Pediatric Pvd: Endotyping and Biomamentioning

confidence: 99%

Addressing the challenges of phenotyping pediatric pulmonary vascular disease

Goss¹,

Mourani

Baker

2017

Pulm. circ.

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Pediatric pulmonary vascular disease (PVD) and pulmonary hypertension (PH) represent phenotypically and pathophysiologically diverse disease categories, contributing substantial morbidity and mortality to a complex array of pediatric conditions. Here, we review the multifactorial nature of pediatric PVD, with an emphasis on improved recognition, phenotyping, and endotyping strategies for pediatric PH. Novel tailored approaches to diagnosis and treatment in pediatric PVD, as well as the implications for long-term outcomes, are highlighted.

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Section: Proteomic Strategies For Pediatric Pvd: Endotyping and Biomamentioning

confidence: 99%

Addressing the challenges of phenotyping pediatric pulmonary vascular disease

Goss¹,

Mourani

Baker

2017

Pulm. circ.

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“…Higher levels of endostatin in tracheal aspirate fluid correlate with parameters reflecting lower lung maturity [20]. A high level of circulating endostatin at birth is associated with the development of BPD in very low birth weight infants [21]. The AP-1 plays an important role in vessel formation, acting on angiogenesis to elicit vessel maturation and integrity [14,22].…”

Section: Discussionmentioning

confidence: 99%

Serial Changes of Serum Endostatin and Angiopoietin-1 Levels in Preterm Infants with Severe Bronchopulmonary Dysplasia and Subsequent Pulmonary Artery Hypertension

Kim

2014

Neonatology

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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.

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“…114 There is evidence that BPD is associated with dysregulation of angiogenesis in the pulmonary vasculature. Evidence in support of this includes: (1) angiogenesis in the lung promotes active alveolarization; 134,137 (2) VEGF and TGF-β signaling are disrupted in BPD; 128,131,164-166 (3) in animal experiments, recombinant VEGF treatment and adenovirus-mediated VEGF gene therapy prevent alveolar injury in BPD; 132,135,136 (4) neonatal treatment with VEGF inhibitor (SU5416) impairs lung growth and decreases nitric oxide production in neonatal rat lungs: 133 in contrast, treatment with inhaled nitric oxide restores lung structure in eNOS-deficient mice; 129 (5) similarly, intraamniotic administration of sVEGFR-1, a potent anti-angiogenic factor, to mice in preterm gestations can decrease the alveolar number, reduce pulmonary vessel density, suppress activation of lung VEGF receptor-2 and increased apoptosis in endothelial and mesenchymal cells in the newborn lung, suggesting that an elevation of anti-angiogenic factors in the amniotic fluid may result in impaired alveolarization and pulmonary vascular growth and contribute to the increased risk of BPD; 167 (6) a high concentration of the anti-angiogenic factor endostatin in umbilical cord blood is associated with the development of BPD in very low birth weight infants; 130 and (7) a significant increase in the expression of endoglin transcript and protein was observed more frequently in the lungs of ventilated preterm infants than in age-matched non-ventilated control lungs. 138 …”

Section: Discussionmentioning

confidence: 99%

Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia

Kim

Romero

Savasan

et al. 2012

American J Rep Immunol

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Objective Cross-talk between inflammation and angiogenesis pathways has been recently reported. The objective of this study was to: 1) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti-angiogenic properties, changes during pregnancy, parturition or intraamniotic infection and/or inflammation (IAI); 2) determine whether an elevation of sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and 3) investigate potential sources of sEng in AF. Study Design A cross-sectional study was conducted to include patients in the following groups: 1) midtrimester (n=20); 2) PTL with term delivery (n=95); 3) PTL leading to preterm delivery with (n=40) and without IAI (n=46); 4) preterm PROM with (n=37) and without IAI (n=37); 5) term in labor (n=48) and not in labor (n=44). AF concentrations of sEng were determined by ELISA. Chorioamniotic membranes, umbilical cord blood and AF macrophages were examined for the expression of endoglin. Results 1) Patients with IAI had a higher median AF concentration of sEng than those without IAI (p=0.02 for PTL; and 0.06 for preterm PROM); 2) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9 respectively); 3) an AF sEng concentration ≥779.5 pg/ml was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); 4) endoglin was co-localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and 5) the concentration of sEng in the supernatant was significantly increased after treatment of macrophages with endotoxin or TNF-α. Conclusions sEng participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes.

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Endostatin Concentration in Cord Plasma Predicts the Development of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

Cited by 36 publications

References 28 publications

Addressing the challenges of phenotyping pediatric pulmonary vascular disease

Addressing the challenges of phenotyping pediatric pulmonary vascular disease

Serial Changes of Serum Endostatin and Angiopoietin-1 Levels in Preterm Infants with Severe Bronchopulmonary Dysplasia and Subsequent Pulmonary Artery Hypertension

Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia

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