Endostatin and Vascular Endothelial Cell Growth Factor (VEGF) in Piglet Lungs: Effect of Inhaled Nitric Oxide and Hyperoxia

Ekekezie, Ikechukwu I; Thibeault, Donald W.; Rezaiekhaligh, Mohammad H.; Norberg, Michael; Mabry, Sherry M; Zhang, Xiaoming; Truog, William E.

doi:10.1203/01.pdr.0000050121.70693.1a

Cited by 27 publications

(22 citation statements)

References 33 publications

(34 reference statements)

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“…Because transition from the intrauterine to extrauterine environment obligates exposure to "relative" hyperoxia, enhanced ELF VEGF could represent a direct effect of the change in ambient O 2 concentration. Exposure of newborn rabbits and 10-day-piglets to >95% O 2 results in increased lung lavage VEGF-A concentrations within 4-5 days of exposure [6,10]. In adult rabbits, the response is more rapid and short-lived, occurring within the first 24 hours of exposure [10].…”

Section: Discussionmentioning

confidence: 99%

“…Rodent and primate models of hyperoxia display similar decrements in VEGF protein and mRNA [6][7][8][9]. During neonatal oxygen injury in the rabbit, VEGF mRNA isoform expression is not only suppressed, but the ratio of VEGF 189 to VEGF 121 mRNA is dramatically reduced [10].…”

Section: Introductionmentioning

confidence: 97%

“…Despite the diminished VEGF expression, hyperoxia often induces a paradoxical rise in VEGF protein obtained from epithelial lining fluid (ELF) [6,10]. Given that plasma concentrations of VEGF are barely detectable during the same period, transudation of plasma VEGF into the alveolar space appears unlikely [6].…”

Section: Introductionmentioning

confidence: 99%

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Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

Shenberger

Zhang

Powell

et al. 2007

Free Radical Biology and Medicine

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Exposure of animals to hyperoxia decreases lung VEGF mRNA expression concomitant with an acute increase in VEGF protein within the epithelial lining fluid (ELF). The VEGF concentration in ELF is in excess of that found in the plasma, leading to the hypothesis that hyperoxia stimulates the release of VEGF protein from stores within the extracellular matrix. To test this hypothesis in a cell culture system, we exposed A549 cells to 95% O 2 for 48 hrs followed by recovery in room air

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

Shenberger

Zhang

Powell

et al. 2007

Free Radical Biology and Medicine

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“…Saugstad (Saugstad, 1988) reported that reoxygenation following hypoxia generated an increase in oxygen free radicals levels that could not be neutralized by antioxidant defences and that resulted in injury to cellular structures. Ekekezie et al (Ekekezie et al, 2003) and Lin et al (Lin et al, 2005) reported that hyperoxia negatively regulates the expression of VEGF, despite recovery in air. These findings are similar to our own.…”

Section: Effects Of Oxidative Stress On Pulmonary Vegf Expression Andmentioning

confidence: 99%

Effects of Oxidative Stress and Antenatal Corticosteroids on the Pulmonary Expression of Vascular Endothelial Growth Factor (VEGF) and Alveolarization

Remesal¹,

Feliciano²,

Ludeña³

2012

Oxidative Stress - Molecular Mechanisms and Biological Effects

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“…However, the reasons that NO improves lung structures are not well defined, a likely hypothesis is that NO promotes angiogenesis (18). This effect is partly mediated via the synthesis of vascular endothelial growth factor (VEGF) (19). In addition, mice deficient in endothelial nitric oxide synthase (eNOS) have been shown to display reduced EPCs mobilization and impaired angiogenesis (20), suggesting that NO may be required for EPC-induced angiogenesis.…”

mentioning

confidence: 99%

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

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Background: Stem cells or inhaled nitric oxide (iNO) are reported to improve lung structures in bronchopulmonary dysplasia (BPD) models. We hypothesized that combined iNO and transplanted endothelial progenitor cells (EPCs) might restore lung structure in rats after neonatal hyperoxia. Methods: Litters were separated into eight groups: room air, hyperoxia, hyperoxia + iNO, hyperoxia + iNO + L-NAME, hyperoxia + EPCs, hyperoxia + EPCs + L-NAME, hyperoxia + EPCs + iNO, and hyperoxia + EPCs + iNO + L-NAME. Litters were exposed to hyperoxia from the 21st day, then, sacrificed. EPCs were injected on the 21st day. L-NAME was injected daily for 7 d from the 21st day. Serum vascular endothelial growth factor (VEGF), radial alveolar count (RAC), VIII factor, EPCs engraftment, lung VEGF, VEGFR2, endothelial nitric oxide (eNOS) and SDF-1 expression, and NO production were examined. results: Hyperoxia exposure led to air space enlargement, loss of lung capillaries, and low expression of VEGF and eNOS. Transplanted EPCs, when combined with iNO, had significantly increased engraftment in lungs, compared to EPCs alone, upon hyperoxia exposure. There was improvement in alveolarization, microvessel density, and upregulation of VEGF and eNOS proteins in the hyperoxia-exposed EPCs with iNO group, compared to hyperoxia alone. conclusion: Combined EPCs and iNO improved lung structures after neonatal hyperoxia. This was associated with the upregulation of VEGF and eNOS expression.B ronchopulmonary dysplasia (BPD) is a chronic lung disease associated with significant mortality and morbidity in premature infants. New BPD is characterized by arrested alveolar and vascular growth (vascular hypothesis of BPD) (1,2). Alveolar formation is a highly coordinated process between the development of airways and pulmonary vasculature (3). Exposure to inflammation caused by excessive O 2 supplementation is hypothesized to interfere with the coordinated process of normal human lung development. Neonatal hyperoxia exposure is known to disrupt alveolar formation and growth, providing a useful model for studying BPD (4).Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD, including embryonic stem cells, mesenchymal stem cells, placental stem cells, umbilical cord stem cells, amniotic fluid and amnionderived cells, and lung progenitor cells. Endothelial progenitor cells (EPCs) are precursors of endothelial cells, which have the capacity of self-renewal and proliferation. EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8). Evidences that angiogenic cells treatment can restore lung structure have been demonstrated. Balasubramaniam et al...

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Endostatin and Vascular Endothelial Cell Growth Factor (VEGF) in Piglet Lungs: Effect of Inhaled Nitric Oxide and Hyperoxia

Cited by 27 publications

References 33 publications

Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

Effects of Oxidative Stress and Antenatal Corticosteroids on the Pulmonary Expression of Vascular Endothelial Growth Factor (VEGF) and Alveolarization

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

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