Ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in ductus arteriosus endothelial cells

Sallmon, Hannes; Akanbi, S.; Weber, Sven C.; Gratopp, Alexander; Rheinländer, Cornelia; Koehne, Petra

doi:10.1017/s1047951117002311

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…The choice of indomethacin or ibuprofen to treat PDA is highly variable among neonatologists and is often influenced by non-clinical factors such as difficulties with drug supply (10)(11)(12). Nevertheless, there are pharmacokinetic, pharmacodynamic and pharmacogenetic differences between ibuprofen and indomethacin that may account for a different response in particular subgroups of preterm infants (72)(73)(74).…”

Section: Discussionmentioning

confidence: 99%

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

González-Luis

Borges-Lujan

Villamor

2022

Preprint

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Endotypes leading to very and extremely preterm birth are clustered into two groups: infection/inflammation and dysfunctional placentation. We conducted a systematic review of observational studies exploring the association between these two endotypes and the pharmacological closure of patent ductus arteriosus (PDA) induced by cyclooxygenase (COX) inhibitors. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for gestational age (SGA) or intrauterine growth restriction. PubMed/Medline and Embase databases were searched. The random-effects odds ratio (OR) and 95% confidence interval (CI) were calculated for each association. We included 30 studies (12639 infants). Meta-analysis showed a significant association between exposure to HDP and increased rate of pharmacological closure of PDA (17 studies, OR 1.41, 95% CI 1.10-1.81, p=0.006). In contrast, neither chorioamnionitis (13 studies, OR 0.75, 95% CI 0.47-1.18, p=0.211) nor SGA (17 studies, OR 1.20, 95% CI 0.96-1.50, p=0.115) were significantly associated with the response to therapy. Subgroup analyses showed that the higher response to COX inhibitors in the HDP group was significant for indomethacin (OR 1.568, 95% CI 1.147-2.141, p=0.005) but not for ibuprofen (OR 1.107, 95% CI 0.248-4.392, p=0.894) or for the studies using both drugs (OR 1.280, 95% CI 0.935-1.751, p=0.124). However, meta-regression showed that this difference between the drugs was not statistically significant (p=404). In conclusion, our data suggest that the pathologic condition that triggers prematurity may alter the response to pharmacological treatment of PDA. The DA of infants exposed to HDP appears to be more responsive to COX inhibitors.

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Section: Discussionmentioning

confidence: 99%

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

González-Luis

Borges-Lujan

Villamor

2022

Preprint

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“…indomethacin did not affect the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. 7 Several authors investigated vascular endothelial growth factor polymorphisms and their potential association with neonatal morbidities such as bronchopulmonary dysplasia, [10][11][12] retinopathy of prematurity, 8,9 and intraventricular haemorrhage 16 in preterm infants. However, the role of the vascular endothelial growth factor polymorphism rs2010963 on patent ductus arteriosus incidence and treatment success rates has not been previously investigated.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 We have recently shown that ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in primary endothelial cells of the rat ductus arteriosus. 7 In addition, several studies discussed vascular endothelial growth factor polymorphisms as potential risk factors for several diseases in neonates, including retinopathy of prematurity 8,9 and bronchopulmonary dysplasia. [10][11][12] The aim of the current study was to investigate the incidence of the vascular endothelial growth factor polymorphism rs2010963 status in a large cohort of preterm infants with and without patent ductus arteriosus and its potential association with cyclooxygenase inhibitor treatment success rates.…”

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confidence: 99%

Vascular endothelial growth factor polymorphism rs2010963 status does not affect patent ductus arteriosus incidence or cyclooxygenase inhibitor treatment success in preterm infants

et al. 2019

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Background:Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults.Aim:Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success.Methods:We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review.Results:We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed.Conclusion:Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.

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Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

2023

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IntroductionEndotypes leading to very and extremely preterm birth are clustered into two groups: infection/inflammation and dysfunctional placentation. We conducted a systematic review of observational studies exploring the association between these two endotypes and the pharmacological closure of patent ductus arteriosus (PDA) induced by cyclooxygenase (COX) inhibitors. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for gestational age (SGA) or intrauterine growth restriction.MethodsPubMed/Medline and Embase databases were searched. The random-effects odds ratio (OR) and 95% confidence interval (CI) were calculated for each association. We included 30 studies (12,639 infants).ResultsMeta-analysis showed a significant association between exposure to HDP and increased rate of pharmacological closure of PDA (17 studies, OR 1.41, 95% CI 1.10–1.81, p = 0.006). In contrast, neither chorioamnionitis (13 studies, OR 0.75, 95% CI 0.47–1.18, p = 0.211) nor SGA (17 studies, OR 1.20, 95% CI 0.96–1.50, p = 0.115) were significantly associated with the response to therapy. Subgroup analyses showed that the higher response to COX inhibitors in the HDP group was significant for indomethacin (OR 1.568, 95% CI 1.147–2.141, p = 0.005) but not for ibuprofen (OR 1.107, 95% CI 0.248–4.392, p = 0.894) or for the studies using both drugs (OR 1.280, 95% CI 0.935–1.751, p = 0.124). However, meta-regression showed that this difference between the drugs was not statistically significant (p = 0.404).Discussion/ConclusionOur data suggest that the pathologic condition that triggers prematurity may alter the response to pharmacological treatment of PDA. The DA of infants exposed to HDP appears to be more responsive to COX inhibitors.

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Ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in ductus arteriosus endothelial cells

Cited by 4 publications

References 20 publications

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

Vascular endothelial growth factor polymorphism rs2010963 status does not affect patent ductus arteriosus incidence or cyclooxygenase inhibitor treatment success in preterm infants

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

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