Plasma vascular endothelial growth factor A and placental growth factor: novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia

Patel, Neil; Moenkemeyer, Florian; Germano, Susie; Cheung, Michael

doi:10.1152/ajplung.00261.2014

Cited by 23 publications

(17 citation statements)

References 40 publications

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“…It is often used in the studies of other diseases such as pregnancy complicated by hypertensive disorders, pulmonary hypertension and preeclampsia [35–37]. Previous study demonstrated that it contributed to angiogenesis and plasma extravasation in ischemia and other pathological conditions [21].…”

Section: Discussionmentioning

confidence: 99%

Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

Yue

Jiang

et al. 2016

Oncotarget

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Previous studies suggest that neurotrophic factors participate in the development of stroke and depression. So we investigated the utility of these biomarkers as predictive and distinguish model for post stroke depression (PSD). 159 individuals including PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control groups were recruited and examined the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors (VEGFR2), placental growth factor (PIGF), insulin-like growth factor (IGF-1) and insulin-like growth factor receptors (IGF-1R). The chi-square test was used to evaluate categorical variable, while nonparametric test and one-way analysis of variance were applied to continuous variables of general characteristics, clinical and biological changes. In order to explore the predictive and distinguish role of these factors in PSD, discriminant analysis and receiver operating characteristic curve were calculated. The four groups had statistical differences in these neurotrophic factors (all P < 0.05) except VEGF concentration and IGF-1R mRNA (P = 0.776, P = 0.102 respectively). We identified these mRNA expression and protein analytes with general predictive performance for PSD and Non-PSD groups [area under the curve (AUC): 0.805, 95% CI, 0.704-0.907, P < 0.001]. Importantly, there is an excellent predictive performance (AUC: 0.984, 95% CI, 0.964-1.000, P < 0.001) to differentiate PSD patients from MDD patients. This was the first study to explore the changes of neurotrophic factors family in PSD patients, the results intriguingly demonstrated that the combination of protein and mRNA expression of biological factors could use as a predictive and discriminant model for PSD.

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Section: Discussionmentioning

confidence: 99%

Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

Yue

Jiang

et al. 2016

Oncotarget

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“…Various growth factor signaling pathways seem to be involved in the pathogenesis of human CDH (6,7,44,60) as well as in the lung response after experimental TO (6,64). Transforming growth factor (TGF)-␤ is a key player in lungbranching morphogenesis and alveolization (5).…”

mentioning

confidence: 99%

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Vuckovic

Herber-Jonat

Flemmer

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-β pathway, a key player in lung development and repair. Pulmonary expression of TGF-β signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-β/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-β transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-β/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.

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“…19,20 Plasma VEGF levels were found elevated and correlated with clinical severity of pulmonary vascular disease in infants with CDH. 21 Furthermore, the authors report a most obvious pattern of increased VEGF in the first week of life in CDH patient, who did not survive and postulate a critical early postnatal period in VEGF-mediated pulmonary vascular development. Our results are rather in accordance with reports of reduced VEGF in infants with acute persistent pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 97%

Are Cytokines Useful Biomarkers to Determine Disease Severity in Neonates with Congenital Diaphragmatic Hernia?

et al. 2016

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This study investigates plasma cytokine levels in neonates with the more common left-sided congenital diaphragmatic hernia (CDH) and correlates them with severity of disease indicated by position of the liver. An intrathoracic part of liver is associated with higher need for extracorporeal membrane oxygenation (ECMO) and higher risk for chronic lung disease (CLD). A total of 28 newborns with CDH were subdivided by their liver position in partially intrathoracic ( = 16) and only abdominal ( = 12) position. Only liver-up patients went on ECMO ( = 9) and developed severe/moderate CLD ( = 5). Controls consisted of 19 healthy matched-term neonates. Laboratory samples were extracted from umbilical cord blood and during the neonatal period. In umbilical cord blood, CDH patients showed decreased IL-8 values while MIP-1a (macrophage inflammatory protein-1) values were increased. Concerning the severity of CDH, we measured significantly higher levels of TGFb2 in CDH patients with liver-up than in liver-down cases and controls ( < 0.006). During the neonatal period, the concentration of IL-10 and vascular endothelial growth factor (VEGF) showed significant deviations in the liver-up group with need for ECMO ( < 0.009). In neonates with CDH, plasma cytokine levels are already altered in utero. TGFb2 may work as an early predictor for severity of disease. VEGF and IL-10 could serve as potential biomarkers predicting the course of disease in CDH.

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Plasma vascular endothelial growth factor A and placental growth factor: novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia

Abstract: Patel N, Moenkemeyer F, Germano S, Cheung MM. Plasma vascular endothelial growth factor A and placental growth factor: novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia.

Cited by 23 publications

References 40 publications

Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

Towards a multi protein and mRNA expression of biological predictive and distinguish model for post stroke depression

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Are Cytokines Useful Biomarkers to Determine Disease Severity in Neonates with Congenital Diaphragmatic Hernia?

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