Hypoxic-Inducible Factors in Neonatal Pulmonary Hypertension

新生儿肺动脉高压的缺氧诱发因素

基本信息

  • 批准号:
    8214146
  • 负责人:
  • 金额:
    $ 6.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-01-01 至 2012-12-31
  • 项目状态:
    已结题

项目摘要

Pulmonary hypertension (PHN) in respiratory distress syndrome (RDS) evolving to bronchopulmonary dysplasia (BPD) results acutely from poor lung inflation and increased blood flow through the patent ductus arteriosus, and chronically from altered reactivity, vascular remodeling, and hypoplasia of the pulmonary vascular bed. The lung develops in relative hypoxia compared to 21% 02 seen at normal term delivery and, especially, to hyperoxia that preterm neonates commonly face. Hypoxia-inducible factors (HIFs) could lower pulmonary artery pressures by modulating surfactant, ductus arteriosus, and pulmonary vascular development. Preliminary data show that HIFs can impact lung expansion at birth, expression of surfactant proteins and lipids, patency of the ductus arteriosus, and angiogenic factors and processes in developing lungs - all of which canmodify pulmonary hypertension. Further data show that HIFs are highly expressed and stable in third trimester fetal primate lungs, while one of them, HIF-1a, declines dramatically after preterm birth. Using cofactors 02, Fe2+, oxoglutarate, and ascorbate, HIF prolyl- hydroxylases (PHDs) specifically regulate HIFstability. We reported that PHDinhibitors (PHDi) profoundly alter stability of HIFs and downstream gene expression (VEGF and its receptors) in lung endothelial and epithelial cells, and fetal lung explants, even in extreme hyperoxia. We hypothesize that PHDi can decrease PHNby restoring the fetal VEGF/eNOS axis and improving perinatal surfactant homeostasis. We propose to examine effects of PHDi delivered antenatally or postnatally, and by differing routes, in ovine models of RDS and persistent PHN in preterm and term ovine models, respectively. Chronically instrumented fetal/neonatal lambs will have pre- and/or postnatal hemodynamic, blood gas, and respiratory physiology measurements. In lung tissue from these animals, we will measure HIFs, HIF- dependent gene products, surfactant proteins and lipids, inflammatory cytokines and cells, and lung morphometry to assess vascular development and remodeling. Results will provide valuable information about pathophysiologic roles of HIFs in perinatal PHN and potential therapeutic uses of PHDi in RDS and PHN.
呼吸窘迫综合征(RDS)发展为支气管肺的肺动脉高压(PHN)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Carl W White其他文献

CXCL17 induces activation of human mast cells via MRGPRX2
CXCL17 通过 MRGPRX2 诱导人类肥大细胞激活
3 ROS : reactive oxygen species RT-qPCR : reverse transcription quantitative PCR SM : sulfur mustard SpO 2 : peripheral oxygen saturation tPA : tissue plasminogen activator
3 ROS : 活性氧 RT-qPCR : 逆转录定量 PCR SM : 硫芥 SpO 2 : 外周血氧饱和度 tPA : 组织纤溶酶原激活剂
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Heidi J. Nick;Carly A Johnson;Amber R. Stewart;Sarah Christeson;A. Leslie;Bloomquist;Amanda S. Appel;A. Donkor;L. Veress;B. Logue;E. Preston;Bratcher;Carl W White
  • 通讯作者:
    Carl W White

Carl W White的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Carl W White', 18)}}的其他基金

Effect of vaping on COVID-19 infection
电子烟对 COVID-19 感染的影响
  • 批准号:
    10176655
  • 财政年份:
    2016
  • 资助金额:
    $ 6.48万
  • 项目类别:
Development of antidotes for toxic gases
有毒气体解毒剂的开发
  • 批准号:
    9145045
  • 财政年份:
    2016
  • 资助金额:
    $ 6.48万
  • 项目类别:
Development of antidotes for toxic gases
有毒气体解毒剂的开发
  • 批准号:
    9564911
  • 财政年份:
    2016
  • 资助金额:
    $ 6.48万
  • 项目类别:
New Developments in Chemical Countermeasures: CounterACT 2018
化学对抗新进展:CounterACT 2018
  • 批准号:
    9490163
  • 财政年份:
    2016
  • 资助金额:
    $ 6.48万
  • 项目类别:
Administration
行政
  • 批准号:
    8115244
  • 财政年份:
    2010
  • 资助金额:
    $ 6.48万
  • 项目类别:
HYPOXIA-INDUCIBLE FACTORS IN BPD
BPD 中的缺氧诱导因素
  • 批准号:
    7716092
  • 财政年份:
    2008
  • 资助金额:
    $ 6.48万
  • 项目类别:
CRITICAL TARGETS IN HYPEROXIC MITOCHONDRIAL INJURY
高氧线粒体损伤的关键目标
  • 批准号:
    7716163
  • 财政年份:
    2008
  • 资助金额:
    $ 6.48万
  • 项目类别:
HYPOXIA-INDUCIBLE FACTORS IN BPD
BPD 中的缺氧诱导因素
  • 批准号:
    7562475
  • 财政年份:
    2007
  • 资助金额:
    $ 6.48万
  • 项目类别:
Novel antioxidant therapeutics for sulfur mustard toxicity (U54)
针对硫芥毒性的新型抗氧化疗法 (U54)
  • 批准号:
    7294907
  • 财政年份:
    2006
  • 资助金额:
    $ 6.48万
  • 项目类别:
Novel therapeutics for vesicants and toxic inhaled chemicals (U54)
针对出疱剂和有毒吸入化学品的新型疗法 (U54)
  • 批准号:
    8737370
  • 财政年份:
    2006
  • 资助金额:
    $ 6.48万
  • 项目类别:

相似海外基金

Un/kindness, shame & resistance: the care of inpatients in NHS adult acute mental health units and how it might be improved
Un/善良,羞耻
  • 批准号:
    2885806
  • 财政年份:
    2023
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Studentship
Post-Acute Care Transitions for Older Adult Medicare Beneficiaries with Serious Mental Illness
患有严重精神疾病的老年医疗保险受益人的急性后护理过渡
  • 批准号:
    10772386
  • 财政年份:
    2023
  • 资助金额:
    $ 6.48万
  • 项目类别:
Paving The Way to a Canadian Standard of Care with CAR-T Cellular Therapy: Phase II Trial of CD19 CAR-T for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia (CLIC-01A)
通过 CAR-T 细胞疗法为加拿大护理标准铺平道路:CD19 CAR-T 治疗复发/难治性成人急性淋巴细胞白血病的 II 期试验 (CLIC-01A)
  • 批准号:
    474619
  • 财政年份:
    2022
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Operating Grants
Investigating the impact acute inhalation of cannabis with a high content of delta-9-tetrahydrocannabinol has on myelination and microglia in adult and aged mice
研究急性吸入高含量 delta-9-四氢大麻酚的大麻对成年和老年小鼠髓鞘形成和小胶质细胞的影响
  • 批准号:
    485965
  • 财政年份:
    2022
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Studentship Programs
Paving The Way to a Canadian Standard of Care with CAR-T Cellular Therapy: Phase II Trial of CD19 CAR-T for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia (CLIC-01A)
通过 CAR-T 细胞疗法为加拿大护理标准铺平道路:CD19 CAR-T 治疗复发/难治性成人急性淋巴细胞白血病的 II 期试验 (CLIC-01A)
  • 批准号:
    466358
  • 财政年份:
    2022
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Operating Grants
Metabolomics for prediction of cisplatin mediated acute kidney injury: a Canadian multi-centre adult and pediatric study
预测顺铂介导的急性肾损伤的代谢组学:加拿大多中心成人和儿童研究
  • 批准号:
    402040
  • 财政年份:
    2019
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Operating Grants
Study of pathogenic mechanism of age-dependent chromosome translocation in adult acute lymphoblastic leukemia
成人急性淋巴细胞白血病年龄依赖性染色体易位发病机制研究
  • 批准号:
    18K16103
  • 财政年份:
    2018
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Causal effect of time-varying driving pressures on mortality in mechanically ventilated, adult patients with acute respiratory distress syndrome
时变驱动压力对机械通气成年急性呼吸窘迫综合征患者死亡率的因果影响
  • 批准号:
    377313
  • 财政年份:
    2017
  • 资助金额:
    $ 6.48万
  • 项目类别:
    Studentship Programs
Role of SETBP1 in adult Ph+ acute lymphoblastic leukemia
SETBP1 在成人 Ph 急性淋巴细胞白血病中的作用
  • 批准号:
    9315111
  • 财政年份:
    2016
  • 资助金额:
    $ 6.48万
  • 项目类别:
Acute Inhibition of Adult-born Granule Cells and its Effect on Antidepressant Act
成体颗粒细胞的急性抑制及其抗抑郁作用
  • 批准号:
    8734273
  • 财政年份:
    2013
  • 资助金额:
    $ 6.48万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了