REGULATION OF THE DUCTUS ARTERIOSUS

动脉导管的调节

• 批准号: 7562419
• 负责人: RONALD I CLYMAN
• 金额: $ 6万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562419
• 关键词: Anatomy; Birth; Bronchopulmonary Dysplasia; Cell Death; Cessation of life; Closure; Computer Retrieval of Information on Scientific Projects Database; Development; Ductus Arteriosus; Event; Funding; Grant; Growth Factor; Human; Hypoxia; Incidence; Indomethacin; Infant; Institution; Left; Mechanical ventilation; Messenger RNA; Migration Assay; Modeling; Morbidity - disease rate; Necrotizing Enterocolitis; Newborn Infant; Nitric Oxide; Papio; Patent Ductus Arteriosus; Patients; Population; Pregnancy; Premature Infant; Process; Prostaglandin Antagonists; Prostaglandins; Regulation; Research; Research Personnel; Resources; Severities; Smooth Muscle Myocytes; Source; Techniques; Testing; United States National Institutes of Health; Week; day; in vivo; migration; postnatal; protein expression; receptor

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. In the premature infant, the ductus arteriosus frequently remains open for many days or weeks after delivery. As many as 70% of newborns delivered prior to 28 weeks gestation will require some form of therapy to close their patient ductus. If left unclosed, a persistent patent ductus arteriosus is associated with significant morbidity: bronchopulmonary dysplasia (with its prolonged need for mechanical ventilation) and necrotizing enterocolitis. Numerous studies have shown that early closure of the ductus arteriosus decreases the severity of bronchopulmonary dysplasia and decreases the incidence of necrotizing enterocolitis. Although inhibitors of prostaglandin synthesis, like indomethacin, induce ductus closure in 85% of preterm infants in whom they are used, ductus reopening occurs in 20-30% of treated infants. Recent studies demonstrate that the postnatal development of ductus wall hypoxia is an essential step in the anatomic remodeling (luminal endothelial proliferation, migration, and smooth muscle cell death) that leads to permanent closure. The studies proposed in this application will examine the mechanisms involved in early, spontaneous ductus closure in the full-term newborn and those involved in the delayed closure of the premature baboon model of persistent patent ductus arteriosus, which is the only model that mimics the long-term events surrounding ductus patency in the preterm human. They will examine the hypothesis that vasoactive factors that alter ductus tone (e.g., prostaglandins, nitric oxide) also interact with an deregulate the growth factors and death factors involved in anatomic remodeling. They will examine mechanisms to increase ductus wall hypoxia in the preterm newborn. They will use immunohistochemical, Western, and Northern techniques to study changes in mRNA and protein expression; they will use assays of cell migration, proliferation, and cell death in isolated vessels, endothelial and smooth muscle cells in culture. They will characterize changes in receptor populations and test their findings in vivo. These studies should increase our understanding of what initiates and sustains the process of ductus closure after birth and why it does not occur in the preterm infant.

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