Retinoic acid enhances lung growth after pneumonectomy

Kaza, Aditya K.; Krön, Irving L.; Kern, John A.; Long, Susan K. De; Fiser, Steven M.; Nguyen, Richard P.; Tribble, Curtis G.; Laubach, Victor E.

doi:10.1016/s0003-4975(01)02478-x

Cited by 65 publications

(56 citation statements)

References 13 publications

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“…Hemotoxylin and eosin (H&E)-stained lung sections were used for morphometric analysis. Lung morphometry was determined using a three-level sampling and point counting technique (18). Measured parameters were total lung volume, total air space volume, total alveolar tissue volume, and total alveolar surface density.…”

Section: Methodsmentioning

confidence: 99%

Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Sakurai¹,

Lee²,

Arsenault³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Methodsmentioning

confidence: 99%

Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Sakurai¹,

Lee²,

Arsenault³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Lung morphometry was performed using a three-level sampling technique described by Davies (4) and Wandel et al (19), a point counting technique described by Gil (7), and as previously described by our laboratory (9). A 42-point test reticule attached to a Nikon Eclipse E400 microscope was used.…”

Section: Methodsmentioning

confidence: 99%

“…IN 1892, IT WAS FIRST DOCUMENTED that after pneumonectomy (removal of a lung) in experimental animals, the remaining lung increases in size (9). This adaptive growth, referred to as compensatory lung growth, results in restoration of lung function and total lung volume, compliance, mass, DNA, protein, alveolar number, and essentially normal lung cell populations (2,3,15).…”

mentioning

confidence: 99%

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Leuwerke

Kaza

Tribble

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS−/−), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS−/− mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS−/− mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth.

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“…The findings that retinoid signaling is required for alveolar development in mice and that retinoid treatment can enhance alveolar development in rats (3)(4)(5) led to vitamin A supplementation of preterm infants at risk of BPD. Some clinical trials of vitamin A supplementation in premature infants have shown no benefit, and others have found that dose is critical (6 -8).…”

mentioning

confidence: 99%

Retinoids Increase Lung Elastin Expression But Fail to Alter Morphology or Angiogenesis Genes in Premature Ventilated Baboons

et al. 2007

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Retinoids regulate elastin synthesis by alveolar myofibroblasts and affect angiogenesis pathways, both of which are processes critical for alveolar development. Retinoids accelerate alveolarization in rodents and are now used therapeutically in premature infants at risk of bronchopulmonary dysplasia (BPD). This study examined the effects of retinoid supplementation on alveolar elastin expression and deposition and angiogenesis-related signaling in a primate model of BPD. Premature baboons delivered at 125 d of gestation after maternal steroid treatment were given surfactant and ventilated with minimal supplemental oxygen for 14 d with (n ϭ 5) and without (n ϭ 5) supplemental vitamin A (5000 U/kg/d) and compared with 140-d unventilated controls. Ventilatory efficiency index (VEI) and oxygenation index (OI) were not statistically different between ventilated treatment groups. Expression of vascular endothelial growth factor A (VEGF-A), fms-related tyrosine kinase 1 (Flt-1), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) was repressed by premature delivery and mechanical ventilation and was not altered by retinoid supplementation. Retinoid supplementation did not enhance alveolar angiogenesis. Elastin expression was repressed by premature delivery and extended ventilation, and retinoid supplementation increased elastin expression specifically in alveolar myofibroblasts within alveolar walls. These results suggest that the small decrease in mortality among premature infants receiving retinoid supplementation may not be mediated through enhanced alveolar development. M any premature infants develop respiratory distress and often require mechanical ventilation and supplemental oxygen to survive. These interventions can perpetuate injury and ultimately lead to altered lung architecture BPD (1), with failed alveolar development, which is a hallmark of BPD (2). The incidence of BPD remains high in infants of very low birth weight despite advancements such as surfactant therapy.The findings that retinoid signaling is required for alveolar development in mice and that retinoid treatment can enhance alveolar development in rats (3-5) led to vitamin A supplementation of preterm infants at risk of BPD. Some clinical trials of vitamin A supplementation in premature infants have shown no benefit, and others have found that dose is critical (6 -8). Tyson et al. (9) found that overall, one additional infant survived without chronic lung disease for every 14 -15 infants who received vitamin A supplements . The mechanism by which vitamin A supplementation may reduce BPD or mortality is not well defined, but may be linked to enhanced alveolar development.The altered alveolar capillary network associated with BPD (10 -12) supports the "vascular hypothesis" that failed capillary development is central to the pathogenesis of BPD (13). Retinoid signaling is required for alveolar capillary development. Vitamin A supplementation may decrease the incidence of BPD by stimulating VEGF expression in alv...

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Retinoic acid enhances lung growth after pneumonectomy

Cited by 65 publications

References 13 publications

Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Retinoids Increase Lung Elastin Expression But Fail to Alter Morphology or Angiogenesis Genes in Premature Ventilated Baboons

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