This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bronchopulmonary Dysplasia (BPD) is a common disease of premature infants who require oxygen and ventilator therapy. At times fatal. BPD probably results from disordered healing if injury to developing lungs. Abnormal microvascular development is characteristic of BPD, leading to insufficient surface for gas exchange. The major goal of this proposal is to investigate expression of Vascular Endothelial Growth Factor (VEGF), a major angiogenic factor that is important for development of the microvasculature The rationale for these studies, based on our preliminary data, are 1) that VEGF expression increases in lung development co-incident with expansion of the alveolar microvasculature, and 2) that hyperoxic injury to developing lung inhibits VEGF expression. Our overall hypothesis is that the development of experimental BPD in the baboon results in disruption of the normal gene program for VEGF expression. Abnormal VEGF expression may be central to the microvascular abnormalities found in BPD. The first Specific Aim investigates the cell-specific expression of VEGF in normal developing baboon lung, using Northern hybridization and in situ hybridization (ISH) combined with immunocytochemistry (ICC). These experiments will also examine the VEGF mRNA splice variants, protein isoforms and VEGF receptors. Using a model of BPD that develops in baboons delivered prematurely at 125 days gestation, the second Specific Aim investigates the hypothesis that VEGF/VEGF receptor expression is decreased when the animals develop BPD. These studies will also examine the VEGF splice variants and protein isoforms. Because extreme hyperoxia inhibits VEGF expression and alters the proportion of splice variants, the third Specific Aim will investigate these factors in a baboon model in which the animals are delivered at 140 days gestation and treated with 100 percent oxygen. VEGF is regulated by the HLF transcription factor, by cell differentiation and by cell proliferation. Using dual ISH and combined ISH/ICC, the fourth Specific Aim examines normal and BPD lungs for these characteristics in VEGF-expressing cells. Because VEGF is a survival factor for endothelial cells and protects them from oxidant injury, these data may lead to a novel therapy for the treatment of the microvascular abnormalities of BPD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR013986-08
Application #
7349769
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
8
Fiscal Year
2006
Total Cost
$22,747
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Shelton, Elaine L; Waleh, Nahid; Plosa, Erin J et al. (2018) Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data. Pediatr Res 84:458-465
Perminov, Ekaterina; Mangosing, Sara; Confer, Alexandra et al. (2018) A case report of ovotesticular disorder of sex development (OT-DSD) in a baboon (Papio spp.) and a brief review of the non-human primate literature. J Med Primatol 47:192-197
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Confer, Alexandra; Owston, Michael A; Kumar, Shyamesh et al. (2018) Multiple endocrine neoplasia-like syndrome in 24 baboons (Papio spp.). J Med Primatol 47:434-439
Mustonen, Allison; Gonzalez, Olga; Mendoza, Elda et al. (2018) Uremic encephalopathy in a rhesus macaque (Macaca mulatta): A case report and a brief review of the veterinary literature. J Med Primatol :
Koistinen, Keith; Mullaney, Lisa; Bell, Todd et al. (2018) Coccidioidomycosis in Nonhuman Primates: Pathologic and Clinical Findings. Vet Pathol 55:905-915
Mahaney, Michael C; Karere, Genesio M; Rainwater, David L et al. (2018) Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance. J Med Primatol 47:3-17
Mangosing, Sara; Perminov, Ekaterina; Gonzalez, Olga et al. (2018) Uterine Tumors Resembling Ovarian Sex Cord Tumors in Four Baboons ( Papio spp.). Vet Pathol 55:753-758
Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T et al. (2018) Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size. Am J Phys Anthropol 165:269-285
Kumar, Shyamesh; Laurence, Hannah; Owston, Michael A et al. (2017) Natural pathology of the captive chimpanzee (Pan troglodytes): A 35-year review. J Med Primatol 46:271-290

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