Prostacyclin concentrations and transitional circulation in preterm infants requiring mechanical ventilation

Kluckow, Martin; Evans, Nick; Leslie, Garth I.; Rowe, Janet

doi:10.1136/fn.80.1.f34

Cited by 12 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To circumvent this problem, we achieved augmentation of PGI 2 production by adenovirus-mediated gene transfer of COX-1 and PGIS. Our results demonstrate that Ad-COP1 infection augmented PGI 2 level to ϳ300 pg/ml, which is within the range of results of clinical studies showing that under various stresses, the PGI 2 level can vary from Ͻ50 to Ͼ500 pg/ml (39,40).…”

Section: Discussionsupporting

confidence: 69%

Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells

Tzu-Ching

Huang

Tam

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hypoxia-inducible factor-1 (HIF-1) takes part in the transcriptional activation of hypoxia-responsive genes. HIF-1␣, a subunit of HIF-1, is rapidly degraded under normoxic conditions by the ubiquitin-proteosome system. Hypoxia up-regulates HIF-1␣ by inhibiting its degradation, thereby allowing it to accumulate to high levels with 3-6 h of hypoxia treatment and decreasing thereafter. In vascular tissues, prostacyclin (prostaglandin I 2 (PGI 2 )) is a potent vasodilator and inhibitor of platelet aggregation and is known as a vasoprotective molecule. However, the role of PGI 2 in HIF-1 activation has not been studied. In the present study, we investigated the effect of PGI 2 on HIF-1 regulation in human umbilical vein endothelial cells under prolonged hypoxia (12 h). Augmentation of PGI 2 via adenovirus-mediated gene transfer of both cyclooxygenase-1 and PGI 2 synthase activated HIF-1 by stabilizing HIF-1␣ in cells under prolonged hypoxia or the hypoxia-normoxia transition but not under normoxia. Exogenous H 2 O 2 abolished PGI 2 -and catalase-induced HIF-1␣ up-regulation, which suggests that degradation of HIF-1␣ under prolonged hypoxia is through a reactive oxygen species-dependent pathway. Moreover, PGI 2 attenuated NADPH oxidase activity by suppressing Rac1 and p47 phox expression under hypoxia. These data demonstrate a novel function of PGI 2 in down-regulating reactive oxygen species production by attenuating NADPH oxidase activity, which stabilizes HIF-1␣ in human umbilical vein endothelial cells exposed to prolonged hypoxia.Hypoxia induces a number of cellular responses, such as angiogenesis, erythropoiesis, and glycolysis, through both gene regulation and post-translational modification of proteins. Hypoxia-inducible factor-1 (HIF-1) 2 takes part in the transcriptional activation of hypoxia-responsive genes through binding to the hypoxia-responsive element (HRE) in the promoter or enhancer regions and activating a number of genes (1-4). HIF-1 is a heterodimer composed of HIF-1␣ and HIF-1␤. HIF-1␣ is rapidly degraded under normoxic conditions by the ubiquitin-proteosome system, whereas HIF-1␤ is constitutively expressed (5). Under hypoxia, HIF-1␣ has been shown to be up-regulated to high levels at 3-6 h and decrease thereafter (6, 7). A number of studies have focused on the mechanism of HIF-1␣ stabilization under hypoxia for 4 -6 h. Recently, a natural antisense HIF-1␣ was suggested to down-regulate HIF-1␣ in A549 cells under prolonged hypoxia (6). However, regulation of HIF-1␣ under prolonged hypoxia (12 h) in endothelial cells remains largely unknown.Under normoxic conditions, HIF-1␣ is regulated through hydroxylation of proline residues by prolyl hydroxylase enzymes (8, 9). The von Hippel-Lindau tumor suppressor protein (pVHL) associates with hydroxylated HIF-1␣ and targets it for ubiquitination and rapid degradation (10). Under hypoxia, prolyl hydroxylase is inactivated through oxygen-sensing mechanisms, and the unmodified HIF-1␣ accumulates, permitting dimerization with HIF-1␤ (3, 11). Various redox-de...

show abstract

Section: Discussionsupporting

confidence: 69%

Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells

Tzu-Ching

Huang

Tam

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This gene is responsible for the production of prostaglandin I2 (prostacyclin), a potent vasodilator which plays a critical role in fetal patency of the ductus arteriosus (reviewed in (25)). It is possible that alterations in the regulation of this gene could lead to abnormal postnatal closure of the DA in a preterm infant, since prostacyclin levels are elevated in preterm infants and the concentration of a prostacyclin metabolite (6-ketoprostaglandin F1-alpha) has been shown to correlate with ductal diameter (26). …”

Section: Discussionmentioning

confidence: 99%

Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants

Dagle¹,

Lepp²,

Cooper³

et al. 2009

Pediatrics

View full text Add to dashboard Cite

Patent ductus arteriosus (PDA) is a common morbidity associated with preterm birth. The incidence of PDA increases with decreasing gestational age to about 70% in infants born at 25 weeks gestation. Although medical treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is used to close the ductus arteriosus, approximately 30% of infants with a PDA do not respond to pharmacologic attempts at closure. We investigated whether single nucleotide polymorphisms (SNPs) in genes that regulate smooth muscle contraction, xenobiotic detoxification, inflammation and other processes are markers for persistent patency of the DA. Initially, 377 SNPs from 130 genes of interest were evaluated in DNA samples collected from 204 infants with a gestational age of less than 32 weeks. A family-based association test (FBAT) was performed on genotyping data to evaluate overtransmission of alleles. P-values of less than 0.01 were detected for genetic variations found in seven genes. The analysis was then replicated with an independent set of 162 infants, focusing on the seven markers with initial p-values less than 0.01, and one genetic variant in the angiotensin II type I receptor (AGTR1) previously shown to be related to PDA. Of the initial positive signals, SNPs in the transcription factor AP-2 beta (TFAP2B) and TNF receptor-associated factor 1 (TRAF1) genes remained significant, both with p-values of 0.005. An AGTR1 polymorphism previously reported to be associated with PDA following prophylactic indomethacin administration was not associated with the presence of a PDA in our population (p = 0.48). Overall, our data support a role for a genetic contribution to the risk of PDAs in preterm infants.

show abstract

“…Because of their importance in the maintenance and control of cerebral hemodynamics, it has previously been suggested that indomethacin may exert its cerebral hemodynamic effects through inhibition of prostanoid production (14,19). Postnatal cerebral hemodynamic adaptation is mediated by changes in prostanoid production (1,11,12,17). It is therefore possible that the cerebral hemodynamic response to indomethacin in the unstable immediate postnatal period will be dependent on the degree to which cerebral hemodynamics have adapted to postnatal life.…”

mentioning

confidence: 99%

Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet

Brown¹,

Lee²,

Kumaran³

et al. 2004

Journal of Applied Physiology

View full text Add to dashboard Cite

With recent discussions in the literature regarding prophylactic use of early (within the first 12 h after birth), low-dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study, we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of indomethacin-treated piglets (9 less than and 7 greater than 13 h of age), Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus. Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets <13 h of age exhibiting delayed increases in cerebral blood flow and cerebral blood volume at 150 min post-indomethacin infusion.

show abstract

Prostacyclin concentrations and transitional circulation in preterm infants requiring mechanical ventilation

Cited by 12 publications

References 20 publications

Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells

Stabilization of Hypoxia-inducible Factor-1α by Prostacyclin under Prolonged Hypoxia via Reducing Reactive Oxygen Species Level in Endothelial Cells

Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants

Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet

Contact Info

Product

Resources

About