Mechanisms of Fetal Myocardial and Coronary Growth Synchrony
胎儿心肌与冠状动脉同步生长的机制
基本信息
- 批准号:9004647
- 负责人:
- 金额:$ 31.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-04-12 至 2018-01-31
- 项目状态:已结题
- 来源:
- 关键词:5&apos-NucleotidaseAdenosineAdultAgeAnatomyAnemiaAreaAutomobile DrivingBedsBiological AssayBlood VesselsBlood capillariesCardiacCardiac MyocytesCardiac developmentCardiac healthCardiovascular DiseasesCause of DeathChemicalsCongenital AbnormalityCoronaryCoronary heart diseaseCritical PathwaysDevelopmentDiagnosisDiseaseEnvironmentEnzymesEpidemiologyEventExpenditureGrowthHeartHeart failureHydrazonesIn VitroIndiumInfarctionInfusion proceduresKDR geneKnowledgeLaboratoriesLeadLengthLifeLinkMitochondriaModelingMolecularMyocardialMyocardiumNeonatalNucleoside TransporterOxygenPathway interactionsPhasePhysiologyPlacental InsufficiencyPregnancyProcessPurinergic P1 ReceptorsRegulationResearchResistanceRisk FactorsRoleSheepSignal TransductionStimulusStressTechniquesTestingTweensUncoupling AgentsUnited StatesVascular Endothelial Growth FactorsWorkbHLH-PAS factor HLFcapillarycardiovascular healthdensityeconomic costfetalfetus hypoxiahypoxia inducible factor 1improvedin uteroin vivoinnovationinstrumentmesoxalonitrilepreventresponse
项目摘要
DESCRIPTION (provided by applicant): The broad, long-term objective of this laboratory is to improve fetal, neonatal and adult cardiac health by discovering the mechanisms regulating cardiac development. Epidemiological research links the adult development of coronary heart disease to events in the fetal period. The relationship between cardiomyocyte and coronary growth in the fetal period ultimately determines maximal coronary reserve, an important risk factor in the adult. Altered fetal myocardial oxygen demand is a common element in normal hearts as it is in conditions of placental insufficiency, fetal hypoxia, congenital malformations that increase cardiac work, and fetal anemia. The driving stimulus synchronizing coronary growth to cardiomyocyte growth in utero is likely to be oxygen, but the underlying mechanisms by which oxygen levels might provide a stimulus for coronary remodeling is not known. Solving this gap in our knowledge would enable us to develop strategies for diagnosing and correcting the cardiomyocyte-capillary mismatch that may underlie vulnerability for disease. We propose that brief periodic mismatches in oxygen demand vs. supply provide signals that link fetal coronary vascular growth to cardiomyocyte growth. We have developed a working model that links coronary to cardiomyocyte growth through specific chemical signals, from which we propose the following specific aims: 1) Determine the degree to which myocardial oxygen demand regulates fetal coronary vascular growth. 2) Determine the degree to which adenosine signaling regulates fetal coronary growth during increased myocardial oxygen demand. 3) Determine how chronically increased oxygen demand potentiates adenosine and VEGF signaling by regulation of pathway components. These aims will be tested in a chronically instrumented fetal sheep model in which cardiac oxygen demand is increased by the innovative application of a mitochondrial uncoupling agent. In order to determine the importance of adenosine signaling for the adaptive process of coronary growth, and adenosine receptor antagonist will also be employed in this model. Coronary reserve will be used to test for coronary growth in vivo, while morphometric techniques will be used to precisely quantify changes in specific vessel beds. Molecular and enzyme assays will be called upon to determine how critical pathways are regulating fetal coronary growth. Understanding the role of myocardial oxygen demand as a determinant of fetal coronary vascular growth will lead to recognition and treatment of fetal conditions that will impact coronary flow reserve and cardiovascular health for life.
描述(由申请人提供):该实验室的广泛,长期目标是通过发现调节心脏发育的机制来改善胎儿,新生儿和成人心脏健康。流行病学研究将成人冠心病的发展与胎儿期的事件联系起来。胎儿期心肌细胞和冠状动脉生长之间的关系最终决定了最大冠状动脉储备,这是成人的一个重要危险因素。改变的胎儿心肌需氧量是正常心脏的常见因素,因为它是在胎盘功能不全,胎儿缺氧,先天性畸形,增加心脏工作,和胎儿贫血的条件。在子宫内,使冠状动脉生长与心肌细胞生长同步的驱动刺激可能是氧气,但氧气水平可能为冠状动脉重塑提供刺激的潜在机制尚不清楚。解决我们知识中的这一差距将使我们能够制定诊断和纠正心肌细胞-毛细血管不匹配的策略,这可能是疾病脆弱性的基础。我们认为,短暂的周期性不匹配的氧气需求与供应提供的信号,胎儿冠状动脉血管生长心肌细胞的生长。我们开发了一个工作模型,通过特定的化学信号将冠状动脉与心肌细胞生长联系起来,从中我们提出了以下具体目标:1)确定心肌需氧量调节胎儿冠状动脉血管生长的程度。2)确定心肌需氧量增加时腺苷信号调节胎儿冠脉生长的程度。3)确定慢性增加的需氧量如何通过调节途径组分增强腺苷和VEGF信号传导。这些目标将在一个长期仪表胎羊模型中进行测试,其中心脏需氧量增加的线粒体解偶联剂的创新应用。为了确定腺苷信号在冠状动脉生长适应性过程中的重要性,腺苷受体拮抗剂也将用于该模型。冠状动脉储备将用于测试体内冠状动脉生长,而形态测量技术将用于精确量化特定血管床的变化。分子和酶检测将被要求确定如何关键途径调节胎儿冠状动脉的生长。了解心肌需氧量作为胎儿冠状动脉血管生长的决定因素的作用,将导致对影响冠状动脉血流储备和心血管健康的胎儿疾病的认识和治疗。
项目成果
期刊论文数量(1)
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 }}
Sonnet Sky Jonker其他文献
Sonnet Sky Jonker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('Sonnet Sky Jonker', 18)}}的其他基金
Role of Birth on Microvasculature Development in Striated MuscleRole of Birth on Microvasculature Development in Striated Muscle
出生对横纹肌微血管发育的作用出生对横纹肌微血管发育的作用
- 批准号:
10341093 - 财政年份:2021
- 资助金额:
$ 31.64万 - 项目类别:
New regulators of lipid metabolism in immature cardiomyocytes
未成熟心肌细胞脂质代谢的新调节因子
- 批准号:
10434904 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Perinatal cardiomyocyte pruning driven by metabolic maturation: Opportunity for intervention
代谢成熟驱动的围产期心肌细胞修剪:干预机会
- 批准号:
9893910 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
New regulators of lipid metabolism in immature cardiomyocytes
未成熟心肌细胞脂质代谢的新调节因子
- 批准号:
9919624 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
New regulators of lipid metabolism in immature cardiomyocytes
未成熟心肌细胞脂质代谢的新调节因子
- 批准号:
10206248 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Perinatal cardiomyocyte pruning driven by metabolic maturation: Opportunity for intervention
代谢成熟驱动的围产期心肌细胞修剪:干预机会
- 批准号:
10566501 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Perinatal cardiomyocyte pruning driven by metabolic maturation: Opportunity for intervention
代谢成熟驱动的围产期心肌细胞修剪:干预机会
- 批准号:
10566503 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Perinatal cardiomyocyte pruning driven by metabolic maturation: Opportunity for intervention
代谢成熟驱动的围产期心肌细胞修剪:干预机会
- 批准号:
10112294 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Perinatal cardiomyocyte pruning driven by metabolic maturation: Opportunity for intervention
代谢成熟驱动的围产期心肌细胞修剪:干预机会
- 批准号:
10356899 - 财政年份:2019
- 资助金额:
$ 31.64万 - 项目类别:
Mechanisms of Fetal Myocardial and Coronary Growth Synchrony
胎儿心肌与冠状动脉同步生长的机制
- 批准号:
8813607 - 财政年份:2012
- 资助金额:
$ 31.64万 - 项目类别:
相似国自然基金
鼠伤寒沙门菌5'-nucleotidase在致病过程中的作用机制研究
- 批准号:
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:
相似海外基金
The Molecular function of ecto 5' nucleotidase in fusion-negative rhabdomyosarcoma
融合阴性横纹肌肉瘤中5端核苷酸酶的分子功能
- 批准号:
10462430 - 财政年份:2022
- 资助金额:
$ 31.64万 - 项目类别:
The Molecular function of ecto 5' nucleotidase in fusion-negative rhabdomyosarcoma
融合阴性横纹肌肉瘤中5端核苷酸酶的分子功能
- 批准号:
10615694 - 财政年份:2022
- 资助金额:
$ 31.64万 - 项目类别:
Combinaisons d’immunothérapies et implication de l'ecto-5'-nucleotidase et de l’infiltration lymphocytaire dans le cancer de la prostate
免疫疗法的组合及其对 5-核酸酶和前列腺癌浸润淋巴细胞的影响
- 批准号:
311752 - 财政年份:2013
- 资助金额:
$ 31.64万 - 项目类别:
Studentship Programs
RELEASE TIME TO STUDY THE PATHWAY OF 5'-NUCLEOTIDASE IN DICTYOSTELIUM
释放时间来研究盘基菌中 5-核苷酸酶的通路
- 批准号:
7381680 - 财政年份:2006
- 资助金额:
$ 31.64万 - 项目类别:
TAGGING GENES AND EXPRESSION OF 5' NUCLEOTIDASE IN DICTYOSTELIUM DISCOIDEUM
盘基网柄菌中标记基因和 5 核苷酸酶的表达
- 批准号:
7381669 - 财政年份:2006
- 资助金额:
$ 31.64万 - 项目类别:
TAGGING GENES AND EXPRESSION OF 5' NUCLEOTIDASE IN DICTYOSTELIUM DISCOIDEUM
盘基网柄菌中标记基因和 5 核苷酸酶的表达
- 批准号:
7170907 - 财政年份:2005
- 资助金额:
$ 31.64万 - 项目类别:
Functional role of CD73/ecto-5'-nucleotidase-derived extracellular adenosine in vascular inflammation (B06)
CD73/ecto-5-核苷酸酶衍生的细胞外腺苷在血管炎症中的功能作用 (B06)
- 批准号:
5352038 - 财政年份:2002
- 资助金额:
$ 31.64万 - 项目类别:
Collaborative Research Centres
MOLECULAR BASIS OF PYRIMIDINE 5'-NUCLEOTIDASE (P5N) DEFICIENCY AND FUNCTIONAL ANALYSIS OF P5N
嘧啶 5-核苷酸酶 (P5N) 缺陷的分子基础及 P5N 的功能分析
- 批准号:
14571001 - 财政年份:2002
- 资助金额:
$ 31.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Acquirement of the Ischemic Cardioprotection and ecto-5'-nucleotidase : Investigation of the Receptor Activation and Subsequent Signal Transduction
缺血性心脏保护和 ecto-5-核苷酸酶的获得:受体激活和随后信号转导的研究
- 批准号:
12470153 - 财政年份:2000
- 资助金额:
$ 31.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The Role of 5'Nucleotidase-expressing Cells in the Regulation of Morphogenesis in Dictyostellium
5核苷酸酶表达细胞在网网柄菌形态发生调控中的作用
- 批准号:
9816664 - 财政年份:1999
- 资助金额:
$ 31.64万 - 项目类别:
Continuing Grant