Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat

Schmidt, Augusto Frederico; Gonçalves, Frances Lilian Lanhellas; Régis, Aline Cristina; Gallindo, Rodrigo Melo; Sbragia, Lourenço

doi:10.1016/j.ajog.2012.04.025

Cited by 33 publications

(29 citation statements)

References 42 publications

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“…The results of fetal lung morphology and are in agreement with previous studies that observed fetuses of progressively smaller size when exposed to nitrofen (N-) and with CDH, pulmonary hypoplasia in both being higher in CDH than in C fetuses 14,29,30 . Ventilation for a short time did not significantly alter this pattern.…”

Section: Discussion Discussion Discussion Discussion Discussionsupporting

confidence: 82%

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

Gallindo

Gonçalves

Figueira

et al. 2014

Rev. Col. Bras. Cir.

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ABSTRACT ABSTRACT ABSTRACTObjective Objective Objective Objective Objective: To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volumecontrolled ventilator. Methods Methods Methods Methods Methods: Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation. Results Results ResultsResults Results: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N-(p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N-and CDH, with no difference between V and N-V (p <0.05). The C and N-groups could be successfully ventilated using a tidal volume of 75 ìl, but the failure of ventilation in the CDH group decreased only when ventilated with 50 ìl. Conclusion Conclusion Conclusion Conclusion Conclusion: Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology.

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Section: Discussion Discussion Discussion Discussion Discussionsupporting

confidence: 82%

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

Gallindo

Gonçalves

Figueira

et al. 2014

Rev. Col. Bras. Cir.

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“…Retinoic acid, a metabolite of retinoin, promotes lung maturation and inhibits androgen receptor levels and function in several organs [24-27]. Further, testosterone has been shown to modulate retinoic acid activity in the lacrimal gland [28].…”

Section: Resultsmentioning

confidence: 99%

miRNA regulated pathways in late stage murine lung development

et al. 2013

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BackgroundMicroRNAs play important roles in regulating biological processes, including organ morphogenesis and maturation. However, little is known about specific pathways regulated by miRNA during lung development. Between the canalicular and saccular stages of the developing lung several important cellular events occur, including the onset of surfactant synthesis, microvascular remodeling and structural preparation for subsequent alveolarization. The miRNAs that are actively regulated, and the identity of their targets during this important developmental interval in the lung remain elusive.ResultsUsing TLDA low density real-time PCR arrays, the expression of 376 miRNAs in male and female fetal mouse lungs of gestational days E15 – E18 were profiled. Statistical analyses identified 25 and 37 miRNAs that changed significantly between sexes and with gestation, respectively. In silico analysis using Ingenuity Pathway Analysis (IPA) identified specific pathways and networks known to be targets of these miRNAs which are important to lung development. Pathways that are targeted by sex regulated miRNAs include retinoin, IGFR1, Tp53 and Akt. Pathways targeted by gestation-regulated miRNAs include VEGFA and mediators of glucose metabolism.ConclusionMiRNAs are differentially regulated across time and between sexes during the canalicular and saccular stages of lung development. Sex-associated differential miRNA expression may regulate the differences in structural and functional male and female lung development, as shown by networks generated using in silico analysis. These data provide a valuable resource to further enhance the understanding of miRNA control of lung development and maturation.

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“…Additionally, 37% of patients on ECMO were neonates with respiratory failure according to the Extracorporeal Life Support Organization’s Registry 2016 report[28]. Given the established roles of VEGF in neonatal lung development[29–31], the use of heparin in this population could also impair lung growth via interfering with VEGF signaling.…”

Section: Discussionmentioning

confidence: 99%

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

et al. 2018

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Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro. Compared to non-heparinized controls, heparinized mice demonstrated impaired pulmonary mechanics, decreased respiratory volumes and flows, and reduced activity levels after left pneumonectomy. They also had lower lung volume, pulmonary septal surface area and alveolar density on morphometric analyses. Lungs of heparinized mice displayed decreased phosphorylation of VEGFR2 compared to the control group, with consequential downstream reduction in markers of cellular proliferation and survival. The use of bivalirudin, an alternative anticoagulant that does not interact with VEGF, preserved lung growth and pulmonary mechanics. These results demonstrated that heparin impairs CLG by reducing VEGFR2 activation. These findings raise concern for the clinical use of heparin in the setting of organ growth or regeneration.

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Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat

Cited by 33 publications

References 42 publications

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

miRNA regulated pathways in late stage murine lung development

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

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