Role of VEGF in Perinatal Hypertension

Summary

Principal Investigator: STEVEN HERBERT ABMAN
Abstract: DESCRIPTION (provided by applicant): Advances in perinatal care, including antenatal steroids, surfactant therapy and improved ventilator strategies, have markedly increased survival of extremely low birth weight infants. However, bronchopulmonary dysplasia (BPD), the chronic lung disease that follows premature birth, remains a major cause of perinatal morbidity and mortality. BPD is a major public health problem, occurring in over 10,000 new cases per year in the USA and causing prolonged hospitalizations, recurrent respiratory exacerbations, impaired lung function into adulthood, exercise intolerance, and pulmonary hypertension in survivors. BPD is characterized by abnormal lung structure due to an arrest of vascular and alveolar growth, but mechanisms contributing to the pathogenesis and optimal treatment of BPD remain poorly understood. Vascular endothelial growth factor (VEGF) is a potent mitogen and critical survival and maintenance factor for lung vascular endothelium. VEGF and its down-stream mediator, nitric oxide (NO), are essential for lung angiogenesis during early embryogenesis, but less is known about its roles and mechanisms of its effects later during development and in the setting of neonatal lung disease. Our past studies have shown that disruption of VEGF - NO signaling causes dysmorphic lung vascular growth and decreased alveolarization in experimental and clinical BPD. Inhibition of angiogenesis impairs alveolarization during lung development, and treatment with VEGF or inhaled NO (iNO) enhances endothelial survival, vascular growth and lung structure in diverse animal models of BPD. However, randomized clinical trials have failed to demonstrate that iNO therapy consistently prevents BPD in human preterm infants, as summarized in a recent NICHD Consensus Conference. Although several issues related to patient selection and study design may account for variability between studies, the failure of iNO therapy to consistently prevent BPD further highlights the importance of developing alternate strategies to preserve endothelial function and angiogenesis in premature infants. Since VEGF treatment improves vascular and alveolar growth in experimental BPD yet has no direct effects on airway epithelium, we hypothesize that in addition to NO activation, VEGF-induced enhancement of lung structure may be mediated through non-NO dependent pathways, and that these pathways may mediate critical epithelial-mesenchymal interactions that are essential for improving lung vascular and alveolar growth in BPD. Based on strong preliminary data, we further hypothesize that the effects of VEGF on lung structure are dependent upon stimulation of hepatocyte growth factor and enhanced retinoic acid production by vascular endothelium ("angiocrine factors"). In this renewal, we propose a series of integrative studies that incorporate physiologic, cell and molecular approaches towards understanding BPD.
Funding Period: 2001-06-20 - 2016-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover
    S Majka
    Department of Medicine, Cardiovascular Pulmonary Research Section, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262, USA
    Am J Physiol Lung Cell Mol Physiol 290:L1183-92. 2006
  2. pmc Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia
    Jen Ruey Tang
    Pediatric Heart Lung Center, Dept of Pediatrics, Univ of Colorado Health Sciences Center, P15 4460A, Mail Stop 8614, 12700 East 19th Ave, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 302:L36-46. 2012
  3. ncbi Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia
    Christopher D Baker
    Paediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO 80045, USA
    Eur Respir J 40:1516-22. 2012
  4. pmc Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep
    Jason Gien
    Department of Neonatology, University of Colorado School of Medicine, Aurora, Colorado, USA
    Pediatr Res 73:252-62. 2013
  5. pmc The NF-κB inhibitory proteins IκBα and IκBβ mediate disparate responses to inflammation in fetal pulmonary endothelial cells
    Jen Ruey Tang
    Department of Pediatrics, Pediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO 80045, USA
    J Immunol 190:2913-23. 2013
  6. pmc Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn
    Cassidy Delaney
    Pediatric Heart Lung Center, Section of Neonatology, University of Colorado Denver, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 304:L894-901. 2013
  7. ncbi Pulmonary vascular disease in bronchopulmonary dysplasia: pulmonary hypertension and beyond
    Peter M Mourani
    Department of Pediatrics, Section of Critical Care, Pediatric Heart Lung Center, University of Colorado, School of Medicine, Aurora, Colorado 80045, USA
    Curr Opin Pediatr 25:329-37. 2013
  8. pmc Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia
    Christopher D Baker
    Pediatric Heart Lung Center, University of Colorado School of Medicine, Mail Stop 8614, 12700 E 19th Ave, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 305:L73-81. 2013
  9. pmc Cord blood endothelial colony-forming cells from newborns with congenital diaphragmatic hernia
    Christopher D Baker
    Pediatric Heart Lung Center, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA
    J Pediatr 163:905-7. 2013
  10. pmc Histologic evidence of intrapulmonary anastomoses by three-dimensional reconstruction in severe bronchopulmonary dysplasia
    Csaba Galambos
    1 Department of Pathology
    Ann Am Thorac Soc 10:474-81. 2013

Detail Information

Publications33

  1. ncbi Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover
    S Majka
    Department of Medicine, Cardiovascular Pulmonary Research Section, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262, USA
    Am J Physiol Lung Cell Mol Physiol 290:L1183-92. 2006
    ....
  2. pmc Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia
    Jen Ruey Tang
    Pediatric Heart Lung Center, Dept of Pediatrics, Univ of Colorado Health Sciences Center, P15 4460A, Mail Stop 8614, 12700 East 19th Ave, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 302:L36-46. 2012
    ..We speculate that impaired VEGF signaling in utero due to exposure of high amniotic fluid levels of sFlt-1 in PE disrupts lung growth and contributes to the increased risk of BPD in infants born to mothers with PE...
  3. ncbi Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia
    Christopher D Baker
    Paediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO 80045, USA
    Eur Respir J 40:1516-22. 2012
    ..Circulating vascular progenitor cells are decreased in the cord blood of preterm infants who develop moderate and severe BPD. These findings suggest that prenatal factors contribute to late respiratory outcomes in preterm infants...
  4. pmc Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep
    Jason Gien
    Department of Neonatology, University of Colorado School of Medicine, Aurora, Colorado, USA
    Pediatr Res 73:252-62. 2013
    ..Endothelin-1 (ET-1) and Rho-kinase (ROCK) increase vascular tone in experimental persistent pulmonary hypertension of the newborn (PPHN). Whether ET-1 activates ROCK to decrease angiogenesis in the developing lung remains unknown...
  5. pmc The NF-κB inhibitory proteins IκBα and IκBβ mediate disparate responses to inflammation in fetal pulmonary endothelial cells
    Jen Ruey Tang
    Department of Pediatrics, Pediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, CO 80045, USA
    J Immunol 190:2913-23. 2013
    ....
  6. pmc Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn
    Cassidy Delaney
    Pediatric Heart Lung Center, Section of Neonatology, University of Colorado Denver, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 304:L894-901. 2013
    ..We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model...
  7. ncbi Pulmonary vascular disease in bronchopulmonary dysplasia: pulmonary hypertension and beyond
    Peter M Mourani
    Department of Pediatrics, Section of Critical Care, Pediatric Heart Lung Center, University of Colorado, School of Medicine, Aurora, Colorado 80045, USA
    Curr Opin Pediatr 25:329-37. 2013
    ....
  8. pmc Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia
    Christopher D Baker
    Pediatric Heart Lung Center, University of Colorado School of Medicine, Mail Stop 8614, 12700 E 19th Ave, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 305:L73-81. 2013
    ..During oxidative stress, preterm ECFC-CM, but not term ECFC-CM, loses its benefit. The inability of term ECFC-CM to promote alveolarization may limit its therapeutic potential. ..
  9. pmc Cord blood endothelial colony-forming cells from newborns with congenital diaphragmatic hernia
    Christopher D Baker
    Pediatric Heart Lung Center, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA
    J Pediatr 163:905-7. 2013
    ..Unlike newborns who develop bronchopulmonary dysplasia, those with congenital diaphragmatic hernia had increased and highly-proliferative cord blood ECFCs. ..
  10. pmc Histologic evidence of intrapulmonary anastomoses by three-dimensional reconstruction in severe bronchopulmonary dysplasia
    Csaba Galambos
    1 Department of Pathology
    Ann Am Thorac Soc 10:474-81. 2013
    ....
  11. pmc Three-dimensional reconstruction identifies misaligned pulmonary veins as intrapulmonary shunt vessels in alveolar capillary dysplasia
    Csaba Galambos
    Department of Pathology and Laboratory Medicine, University of Colorado School of Medicine and Children s Hospital Colorado, Aurora, CO Pediatric Heart Lung Center, University of Colorado School of Medicine and Children s Hospital Colorado, Aurora, CO
    J Pediatr 164:192-5. 2014
    ..Using 3-dimensional reconstruction of ACD/MPV lung tissue, we report that the veins in MPV are intrapulmonary shunt vessels, and speculate that MPV contributes to the poor prognosis. ..
  12. pmc Pulmonary artery endothelial cell dysfunction and decreased populations of highly proliferative endothelial cells in experimental congenital diaphragmatic hernia
    Shannon N Acker
    Univ of Colorado School of Medicine, 12631 E 17th Ave, C302, Aurora, CO 80045
    Am J Physiol Lung Cell Mol Physiol 305:L943-52. 2013
    ..We conclude that surgically induced CDH in fetal sheep causes endothelial dysfunction and marked reduction of the HP-PAEC population. We speculate that this CDH PAEC phenotype contributes to impaired vascular growth in CDH. ..
  13. pmc Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension
    David Wolf
    Perinatal Research Facility, 13243 E 23rd Ave, Mail Stop F441, Aurora, CO 80045
    Am J Physiol Lung Cell Mol Physiol 306:L361-71. 2014
    ..We speculate that therapies aimed at decreasing ET-1 production will restore PPARγ signaling, preserve endothelial function, and improve angiogenesis in PPHN. ..
  14. pmc Peroxisome proliferator activated receptor-γ-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension
    Jason Gien
    Perinatal Research Facility, 13243 E 23rd Ave, Mail Stop F441, Aurora, CO 80045
    Am J Physiol Lung Cell Mol Physiol 306:L299-308. 2014
    ..Restoring normal PPARγ-ROCK signaling may prevent vascular remodeling and improve outcomes in PPHN. ..
  15. pmc Effects of early inhaled nitric oxide therapy and vitamin A supplementation on the risk for bronchopulmonary dysplasia in premature newborns with respiratory failure
    Monika M Gadhia
    Division of Neonatology, Department of Pediatrics, Weill Cornell Medical College, New York, NY Electronic address
    J Pediatr 164:744-8. 2014
    ..To assess whether the combination of early inhaled nitric oxide (iNO) therapy and vitamin A supplementation lowers the incidence of bronchopulmonary dysplasia (BPD) in premature newborns with respiratory failure...
  16. pmc Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus
    Cassidy Delaney
    Pediatric Heart Lung Center, Aurora, CO, USA
    Am J Physiol Lung Cell Mol Physiol 301:L937-44. 2011
    ..We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation...
  17. pmc Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep
    Paul J Rozance
    Division of Neonatology, Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, USA
    Am J Physiol Lung Cell Mol Physiol 301:L860-71. 2011
    ..We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR...
  18. pmc Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension
    Marc Chester
    Pediatric Heart Lung Center, Sections of Neonatology and Pulmonary Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
    Am J Physiol Lung Cell Mol Physiol 301:L755-64. 2011
    ..We speculate that increased NO-insensitive sGC may contribute to the pathogenesis of PPHN, and cinaciguat may provide a novel treatment of severe pulmonary hypertension...
  19. ncbi BAY 41-2272, a direct activator of soluble guanylate cyclase, reduces right ventricular hypertrophy and prevents pulmonary vascular remodeling during chronic hypoxia in neonatal rats
    Philippe Deruelle
    Department of Pediatrics, Pediatric Heart Lung Center, University of Colorado School of Medicine, Denver, Colo, USA
    Biol Neonate 90:135-44. 2006
    ..We speculate that BAY 41-2272 may provide a new therapy for chronic PH...
  20. pmc Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease
    Bernard Thebaud
    Department of Pediatrics, Division of Neonatology, Vascular Biology Group, University of Alberta, HMRC 407, Edmonton, AB, T6G 2S2, Canada
    Am J Respir Crit Care Med 175:978-85. 2007
    ....
  21. pmc Intrauterine pulmonary hypertension impairs angiogenesis in vitro: role of vascular endothelial growth factor nitric oxide signaling
    Jason Gien
    Section of Neonatology, Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA
    Am J Respir Crit Care Med 176:1146-53. 2007
    ..Mechanisms that impair angiogenesis in neonatal persistent pulmonary hypertension (PPHN) are poorly understood...
  22. ncbi Early inhaled nitric oxide treatment decreases apoptosis of endothelial cells in neonatal rat lungs after vascular endothelial growth factor inhibition
    Jen Ruey Tang
    Pediatric Heart Lung Center, Dept of Pediatrics, Univ of Colorado Health Sciences Center, Mail Stop 8317, 12800 E 19th Ave, PO Box 6511, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 293:L1271-80. 2007
    ..Early iNO treatment after VEGF inhibition reduces endothelial cell apoptosis in neonatal lungs. We speculate that enhancing endothelial cell survival after lung injury may preserve neonatal lung growth in bronchopulmonary dysplasia...
  23. ncbi Impaired VEGF and nitric oxide signaling after nitrofen exposure in rat fetal lung explants
    Vincent Muehlethaler
    Pediatric Heart Lung Center, Dept of Pediatrics, Univ of Colorado School of Medicine and The Children s Hospital, Mail Stop 8317, PO Box 6511, Aurora, CO 80045 USA
    Am J Physiol Lung Cell Mol Physiol 294:L110-20. 2008
    ..Disruption of lung architecture after VEGF receptor blockade was similar to nitrofen-induced changes but was more responsive to NO...
  24. pmc Chronic intrauterine pulmonary hypertension increases endothelial cell Rho kinase activity and impairs angiogenesis in vitro
    Jason Gien
    Department of Pediatrics, University of Colorado School of Medicine, Denver, CO, USA
    Am J Physiol Lung Cell Mol Physiol 295:L680-7. 2008
    ..We conclude that Rho kinase activity is increased in PPHN PAECs and impairs angiogenesis and downregulates eNOS protein and NO production in vitro...
  25. pmc Fasudil inhibits the myogenic response in the fetal pulmonary circulation
    Pierre Tourneux
    The Pediatric Heart Lung Center, Sections of Neonatology and Pulmonary Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
    Am J Physiol Heart Circ Physiol 295:H1505-13. 2008
    ..001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation...
  26. ncbi Role of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension
    Steven H Abman
    Pediatric Heart Lung Center, University of Colorado School of Medicine and The Children s Hospital, Aurora, Colorado 80045, USA
    Annu Rev Med 60:13-23. 2009
    ..This article briefly reviews preclinical data and the current status of ETRAs in the clinical management of PAH...
  27. pmc Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus
    Marc Chester
    Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, 80045, USA
    Am J Physiol Lung Cell Mol Physiol 297:L318-25. 2009
    ....
  28. pmc Endothelial colony-forming cells from preterm infants are increased and more susceptible to hyperoxia
    Christopher D Baker
    Pediatric Heart Lung Center, University of Colorado, Denver School of Medicine, Aurora, CO 80045, USA
    Am J Respir Crit Care Med 180:454-61. 2009
    ..Endothelial progenitor cells, such as self-renewing highly proliferative endothelial colony-forming cells (ECFCs), may participate in vascular repair. The effect of hyperoxia on ECFC growth is unknown...
  29. pmc Hyperoxia disrupts vascular endothelial growth factor-nitric oxide signaling and decreases growth of endothelial colony-forming cells from preterm infants
    Hideshi Fujinaga
    Pediatric Heart Lung Center Univ of Colorado Denver School of Medicine, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 297:L1160-9. 2009
    ..NO treatment also increases growth during hyperoxia. Exogenous VEGF or NO may protect preterm ECFCs from the adverse effects of hyperoxia and preservation of ECFC function may improve outcomes of preterm infants...
  30. pmc Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice
    Vivek Balasubramaniam
    Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado Denver, 12800 E 19th Ave, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 298:L315-23. 2010
    ..We conclude that treatment with BMDAC after neonatal hyperoxia restores lung structure in this model of bronchopulmonary dysplasia...
  31. pmc Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin
    Jen Ruey Tang
    Dept of Pediatrics, Univ of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Am J Physiol Lung Cell Mol Physiol 299:L735-48. 2010
    ..Moreover, moderate postnatal hyperoxia after antenatal ETX restores lung growth and prevents pulmonary hypertension during infancy...
  32. pmc Recent progress in understanding pediatric pulmonary hypertension
    Steven H Abman
    Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado School of Medicine and Children s Hospital, Aurora, Colorado, USA
    Curr Opin Pediatr 23:298-304. 2011
    ..Advances in pulmonary vascular biology over the past few decades have significantly expanded therapeutic strategies; however, many unique issues persist regarding our understanding of pediatric PAH...
  33. pmc Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia
    Erica Mandell
    Dept of Pediatrics, The Children s Hospital, B395, 13123 East 16th Ave, Aurora, CO 80045
    Am J Physiol Lung Cell Mol Physiol 306:L420-8. 2014
    ..We conclude that antenatal vit D therapy improved oxygenation and survival in newborn rat pups and enhanced late lung structure after exposure to IA ETX in vivo, which may partly be due to direct effects on vascular and alveolar growth...

Research Grants30

  1. The unique role of IkBa in modulating NF-kB activity in the newborn lung.
    CLYDE JASON WRIGHT; Fiscal Year: 2013
    ..Interventions aimed at preventing the development of BPD will reduce the impact of this major public health burden. ..
  2. Neonatal Oxygen and Susceptibility to Respiratory Viral Infections
    MICHAEL A O'REILLY; Fiscal Year: 2013
    ..By integrating research findings in mice and humans, we hope to ultimately identify novel therapeutic opportunities for improving the health of children born prematurely. ..
  3. Role of VEGF in lung development and hyperoxic injury
    Americo E Esquibies; Fiscal Year: 2013
    ..My ultimate goal is to design strategies to treat preterm infants who are at risk for BPD in a manner that promotes normal lung development in the face of therapeutic interventions including supplemental oxygen . ..
  4. Trial Of Late SURFactant (TOLSURF) to Prevent BPD-Data Coordinating Center
    Dennis M Black; Fiscal Year: 2013
    ..This research has potential to decrease chronic infant lung disease and asthma, important areas of public health, reduce cost of care, and improve long-term outcome for premature infants. ..
  5. Role of Fetal Lung Macrophages in Bronchopulmonary Dysplasia
    Lawrence S Prince; Fiscal Year: 2013
    ..These processes contribute to the pathogenesis of bronchopulmonary dysplasia, a chronic lung disease that affects up to 10,000 former preterm children each year in the United States. (End of Abstract) ..
  6. Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr
    ROBERTA ANDERSON BALLARD; Fiscal Year: 2013
    ..This research has potential to decrease chronic infant lung disease and asthma, important areas of public health, reduce cost of care, and improve long-term outcome for premature infants. ..
  7. Assessment of lung function in neonates and infants
    IULIAN CONSTANTIN RUSET; Fiscal Year: 2013
    ..One subject will be a neonate born prematurely who has early BPD. The second subject will be a neonate under care due to an hypoxic ischemic event. This subject's lungs should be structurally normal. ..
  8. Pulmonary Blood Flow in Lung Development and Congenital Diaphragmatic Hernia
    Douglas A Potoka; Fiscal Year: 2013
    ....
  9. Spinal Cord Injury, Plasticity and Transplant Mediated Repair
    John D Houle; Fiscal Year: 2013
    ..This Program Project has direct relevance to the design and implementation of future treatment programs for acute and delayed intervention after SCI. ..
  10. MECHANISMS OF BPD PATHOGENESIS
    PARVIZ MINOO MINOO; Fiscal Year: 2013
    ..As in Specific Aim 1, the focus of the mechanisms in this aim will be the PI3k/Akt/Erk pathway. ..
  11. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
    ..3. Recruit promising junior investigators and provide mentoring by established NIH-funded researchers. 4. Support a multidisciplinary research program led by junior investigators in translational infectious diseases immunology. ..
  12. Expanding Excellence in Developmental Biology in Oklahoma
    Linda F Thompson; Fiscal Year: 2013
    ..abstract_text> ..
  13. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
    ..abstract_text> ..
  14. MITOCHONDRIAL ENCEPHALOMYOPATHIES AND MENTAL RETARDATION
    Salvatore DiMauro; Fiscal Year: 2013
    ....
  15. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013
    ..This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity. ..
  16. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
    ..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..
  17. Foxf1 Transcription Factor in Development of Pulmonary Capillaries
    Vladimir V Kalinichenko; Fiscal Year: 2013
    ....
  18. UCSF Clinical Research Center for Prematurity and Respiratory Outcomes Program
    Roberta L Keller; Fiscal Year: 2013
    ..The findings will suggest new predictors and potential therapies to improve long-term outcome for infants at high risk of lung disease. ..
  19. Biomarkers of Immunologic Function and Preterm Respiratory Outcomes
    Alan H Jobe; Fiscal Year: 2013
    ..These evaluations are directed toward biomarkers to predict disease severity and 1 yr. outcomes with a goal of developing new treatment strategies. ..
  20. Improving Prematurity-related Respiratory Outcomes at Vanderbilt (IMPROV)
    JUDY LYNN ASCHNER; Fiscal Year: 2013
    ....
  21. Cell Survival and Death in Oxidant Lung Injury
    MICHAEL A O'REILLY; Fiscal Year: 2013
    ....