Fetal Programming of Coronary Artery Disease

冠状动脉疾病的胎儿编程

基本信息

  • 批准号:
    6617261
  • 负责人:
  • 金额:
    $ 14.01万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-05-02 至 2006-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the United States and other developed countries. In the United States alone, approximately 1 million individuals die from cardiovascular disease each year, nearly 50% of deaths from all causes. In addition to known associated risk factors for cardiovascular disease studies from the last decade suggest that influences during fetal life may predispose to coronary heart disease. There exist a number of potential mechanisms linking fetal adaptations to maternal and environmental influences to cardiovascular disease, including alterations in metabolic and endocrine functions, organ and tissue structure and gene expression. The renin-angiotensin system has been closely linked the development of endothelial dysfunction and progression to atherosclerosis. Previous studies of fetal programming demonstrate upregulation of key genes of the renin-angiotensin system and enhanced action of angiotensin II. We hypothesize that upregulation of the renin-angiotensin system in the coronary vasculature is an important aspect of fetal programming, resulting in increased oxidative stress and ultimately coronary endothelial dysfunction and coronary artery disease. We plan to use a developed model of fetal programming namely early prenatal exposure to dexamethasone in fetal sheep to further explore this hypothesis. Increased fetal exposure to glucocorticoids resulting from environmental influences on placental function appears to be an important mechanism of fetal programming. The specific aims of this proposal are to demonstrate that following prenatal exposure to dexamethasone, 1) coronary artery angiotensin II receptor gene expression is upregulated, 2) coronary vascular reactivity is altered, particularly in response to angiotensin, 3) vascular oxidative stress is enhanced, and 4) vascular gene expression profiles differ. We propose these differences are present early in life and persist throughout development. Studies of the effects of early dexamethasone exposure on coronary vascular function and vascular gene expression may provide an important link between adverse intrauterine environment and the subsequent development of atherosclerosis. Understanding these links and the specific mechanisms by which the altered fetal environment leads to disease in adulthood has important, worldwide public health implications. Only when the causes and mechanisms of hypertension and cardiovascular disease are understood in the context of a developmental process will it be possible to develop strategies for primary prevention.
描述(由申请人提供):心血管疾病是美国和其他发达国家的主要死亡原因。仅在美国,每年约有100万人死于心血管疾病,占所有原因死亡人数的近50%。除了已知的心血管疾病相关危险因素外,过去十年的研究表明,胎儿期的影响可能易患冠心病。存在许多将胎儿适应母体和环境影响与心血管疾病联系起来的潜在机制,包括代谢和内分泌功能、器官和组织结构以及基因表达的改变。肾素-血管紧张素系统与内皮功能障碍的发展和动脉粥样硬化的进展密切相关。以前的研究表明,胎儿编程上调的关键基因的肾素-血管紧张素系统和增强的行动血管紧张素II。我们假设,在冠状动脉血管系统中的肾素-血管紧张素系统的上调是胎儿编程的一个重要方面,导致氧化应激增加,最终冠状动脉内皮功能障碍和冠状动脉疾病。我们计划使用一种成熟的胎儿编程模型,即胎羊早期产前暴露于地塞米松,以进一步探讨这一假设。环境对胎盘功能的影响导致胎儿暴露于糖皮质激素的增加似乎是胎儿编程的一个重要机制。本提案的具体目的是证明产前暴露于地塞米松后,1)冠状动脉血管紧张素II受体基因表达上调,2)冠状动脉血管反应性改变,特别是对血管紧张素的反应,3)血管氧化应激增强,4)血管基因表达谱不同。我们认为这些差异存在于生命的早期,并在整个发展过程中持续存在。研究早期地塞米松暴露对冠状动脉血管功能和血管基因表达的影响可能提供不良宫内环境和随后动脉粥样硬化发展之间的重要联系。了解这些联系以及胎儿环境改变导致成年期疾病的具体机制具有重要的全球公共卫生意义。只有在发展过程的背景下了解高血压和心血管疾病的原因和机制,才有可能制定一级预防策略。

项目成果

期刊论文数量(0)
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JEFFREY L SEGAR其他文献

JEFFREY L SEGAR的其他文献

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{{ truncateString('JEFFREY L SEGAR', 18)}}的其他基金

Theophylline Prophylaxis during Hypothermia to Limit Neonatal Nephron Damage
低温期间预防茶碱以限制新生儿肾单位损伤
  • 批准号:
    10656030
  • 财政年份:
    2023
  • 资助金额:
    $ 14.01万
  • 项目类别:
Regulation of Fetal Myocyte Development
胎儿肌细胞发育的调节
  • 批准号:
    7564047
  • 财政年份:
    2007
  • 资助金额:
    $ 14.01万
  • 项目类别:
Regulation of Fetal Myocyte Development
胎儿肌细胞发育的调节
  • 批准号:
    7745510
  • 财政年份:
    2007
  • 资助金额:
    $ 14.01万
  • 项目类别:
Regulation of Fetal Myocyte Development
胎儿肌细胞发育的调节
  • 批准号:
    7337326
  • 财政年份:
    2007
  • 资助金额:
    $ 14.01万
  • 项目类别:
Regulation of Fetal Myocyte Development
胎儿肌细胞发育的调节
  • 批准号:
    7195220
  • 财政年份:
    2007
  • 资助金额:
    $ 14.01万
  • 项目类别:
Fetal Programming of Coronary Artery Disease
冠状动脉疾病的胎儿编程
  • 批准号:
    6745086
  • 财政年份:
    2003
  • 资助金额:
    $ 14.01万
  • 项目类别:
Fetal Programming of Coronary Artery Disease
冠状动脉疾病的胎儿编程
  • 批准号:
    6864446
  • 财政年份:
    2003
  • 资助金额:
    $ 14.01万
  • 项目类别:
Fetal Cardiac Hypertrophy: Vascular/Metabolic Adaptation
胎儿心脏肥大:血管/代谢适应
  • 批准号:
    6537789
  • 财政年份:
    2001
  • 资助金额:
    $ 14.01万
  • 项目类别:
Fetal Cardiac Hypertrophy: Vascular/Metabolic Adaptation
胎儿心脏肥大:血管/代谢适应
  • 批准号:
    6638630
  • 财政年份:
    2001
  • 资助金额:
    $ 14.01万
  • 项目类别:
Fetal Cardiac Hypertrophy: Vascular/Metabolic Adaptation
胎儿心脏肥大:血管/代谢适应
  • 批准号:
    6740793
  • 财政年份:
    2001
  • 资助金额:
    $ 14.01万
  • 项目类别:

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