Endothelin-1 and<scp>L</scp>-Arginine in Preterm Infants with Respiratory Distress

Rifay, Amira S. El; Sherif, Lobna S.; Said, Reem N.; Elwakkad, Amany; EL-Refay, Amira; Aly, Hany

doi:10.1055/s-0030-1263295

Cited by 18 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In newborn infants with respiratory distress syndrome (RDS), the degree of elevation in plasma ET-1 concentrations predicted higher risk for the subsequent development of BPD (19,49). In newborn lambs with RDS and PPHN, as well as human infants with PPHN and CDH, plasma ET-1 levels predict disease severity and degree of pulmonary hypertension (15,34,53).…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension

Wolf

Tseng

Seedorf

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Increased endothelin-1 (ET-1) disrupts angiogenesis in persistent pulmonary hypertension of the newborn (PPHN), but pathogenic mechanisms are unclear. Peroxisome proliferator activated receptor γ (PPARγ) is decreased in adult pulmonary hypertension, but whether ET-1-PPARγ interactions impair endothelial cell function and angiogenesis in PPHN remains unknown. We hypothesized that increased PPHN pulmonary artery endothelial cell (PAEC) ET-1 production decreases PPARγ signaling and impairs tube formation in vitro. Proximal PAECs were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. PPARγ and phospho-PPARγ protein were compared between normal and PPHN PAECs ± ET-1 and bosentan (ETA/ETB receptor blocker). Tube formation was assessed in response to PPARγ agonists ± ET-1, N-nitro-l-arginine (LNA) (NOS inhibitor), and PPARγ siRNA. Endothelial NO synthase (eNOS), phospho-eNOS, and NO production were measured after exposure to PPARγ agonists and PPARγ siRNA. At baseline, PPHN PAECs demonstrate decreased tube formation and PPARγ protein expression and activity. PPARγ agonists restored PPHN tube formation to normal. ET-1 decreased normal and PPHN PAEC tube formation, which was rescued by PPARγ agonists. ET-1 decreased PPARγ protein and activity, which was prevented by bosentan. PPARγ agonists increased eNOS protein and activity and NO production in normal and PPHN PAECs. LNA inhibited the effect of PPARγ agonists on tube formation. PPARγ siRNA decreased eNOS protein and tube formation in normal PAECs. We conclude that ET-1 decreases PPARγ signaling and contributes to PAEC dysfunction and impaired angiogenesis in PPHN. We speculate that therapies aimed at decreasing ET-1 production will restore PPARγ signaling, preserve endothelial function, and improve angiogenesis in PPHN.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension

Wolf

Tseng

Seedorf

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…ET-1 also contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy characterized by decreased alveolar and vascular growth. In newborn infants with RDS, the degree of elevation in plasma ET-1 concentrations predicted higher risk for the subsequent development of BPD (28,29). Past work further suggests that lung fibrosis in BPD may also be ET-1 dependent (30).…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep

et al. 2012

View full text Add to dashboard Cite

Background Endothelin-1 (ET-1) and rho-kinase (ROCK) increase vascular tone in experimental PPHN but whether ET-1 activates ROCK to decrease angiogenesis in the developing lung remains unknown. Methods Proximal PAEC were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and age matched controls. Growth and tube formation were assessed after ET-1 treatment. The effect of ET-1 antagonism on tube formation was studied using ET-1 SiRNA, ET-1 monoclonal antibody (ET-1 mAb), BQ-123 (ETA blocker) and bosentan (ETA/ETB blocker). ET-1 gene and protein and ETA/ETB receptor protein expression were measured in normal and PPHN PAECs. ET-1-ROCK interactions were assessed by measuring ROCK activity after ET-1, ET-1 SiRNA and bosentan treatments and tube formation with ET-1 and Y-27632 (ROCK inhibitor). Results ET-1 had no effect on growth, but decreased tube formation in normal and PPHN PAEC. PPHN decreased tube formation in PAEC. ET-1 protein and gene expression were increased and ETB receptor protein decreased in PPHN PAECs. ET-1 SiRNA, ET-1mAb, and bosentan, but not BQ-123, increased tube formation. ROCK activity was increased in PPHN PAECs, and decreased with ET-1 SiRNA and bosentan treatments. Y-27632 prevented the decrease in tube formation with ET-1. Conclusion ET-1 impairs angiogenesis of fetal PAECs through ROCK activation. Disruption of ET-1 ROCK interactions may increase vascular growth in PPHN.

show abstract

“…Endothelin-1 (ET-1) is an endogenous vasoconstrictive peptide, which is involved in the pathogenesis of various lung disorders such as pulmonary hypertension, acute respiratory failure and pulmonary fibrosis [2]. In preterm newborns, raised plasma ET-1 levels have been related to the development of respiratory distress syndrome [3] whereas an early increase of ET-1 in the tracheal aspirate has been shown to correlate with subsequent progression to BPD [4]. In addition, the antiangiogenic effect of ET-1 has been linked to the pathogenesis of BPD [5] and evidence from human ex vivo models suggests that ET-1 signaling may play a critical role in the development of a BPD-like fibrotic process in the immature lung [6].…”

Section: Introductionmentioning

confidence: 99%

Plasma Proendothelin-1 as an Early Marker of Bronchopulmonary Dysplasia

Baumann¹,

Fouzas

Pramana

et al. 2015

Neonatology

View full text Add to dashboard Cite

Background: Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. Clinical prediction of BPD at an early stage in life is difficult. Plasma proendothelin-1 (CT-proET-1) is a lung injury biomarker in pulmonary hypertension and respiratory distress. Objective: To assess the prognostic ability of CT-proET-1 in BPD. Methods: In 227 prospectively enrolled preterm infants born at <32 weeks gestational age (GA), plasma CT-proET-1 was measured at birth, day of life (DOL) 2, 3, 6 and 28, and at 36 weeks postmenstrual age (PMA). BPD was defined as mild in infants requiring supplemental oxygen at DOL 28 and moderate/severe in those requiring it at 36 weeks PMA. Results: The predictive ability of CT-proET-1 for any BPD was poor at birth [area under the ROC curve (AUC) 0.654, 95% CI 0.494-0.814], moderate at DOL 2 and 3 (AUC 0.769, 95% CI 0.666-0.872) and excellent at DOL 6 (AUC 0.918, 95% CI 0.840-0.995). Multivariable regression analysis revealed that CT-proET-1 levels at DOL 2, 3, 6 and 28 were strongly related to the duration of oxygen supplementation, independently of GA and the duration of respiratory support. Conclusions: CT-proET-1 is a novel promising biomarker for predicting the development of BPD in preterm infants when measured at the end of the first week of life.

show abstract

Endothelin-1 andL-Arginine in Preterm Infants with Respiratory Distress

Cited by 18 publications

References 33 publications

Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension

Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension

Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep

Plasma Proendothelin-1 as an Early Marker of Bronchopulmonary Dysplasia

Contact Info

Product

Resources

About