GENETICS AND INTERMITTENT MYOCARDIAL HYPOXIA
遗传学与间歇性心肌缺氧
基本信息
- 批准号:6233708
- 负责人:
- 金额:$ 25.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-09-30 至 2004-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The overall objective is to localize the gene(s) responsible for
susceptibility to myocardial ischemia caused by intermittent hypoxia and
characterize the physiology in a novel model system. Patients with
obstructive sleep apnea have an increased cardiovascular morbidity and
mortality. Diseases such as hypertension, hyperlipidemia and diabetes
mellitus have an underlying genetic basis and represent risk factors for
ischemic heart disease. However, the genetic components(s) underlying the
impact of intermittent hypoxia on susceptibility to myocardial ischemia are
unknown. It is hypothesized that genetic factors are responsible for
increased susceptibility to myocardial ischemia caused by intermittent hypoxia
in Dahl S rats compared with Brown Norway rats. This hypothesis will be
tested by crossing the Brown Norway with Dahl S rat. The isolated heart model
and coronary vessels will be used to facilitate discrete, well-controlled
investigations of susceptibility to ischemia with and without prior
intermittent hypoxia. A total genome scan will be performed to map
quantitative trait loci (QTLs) involved in adaption to intermittent hypoxia
and susceptibility to myocardial ischemia. Phenotypic difference between
parents and the congenic derivatives resulting form ischemia and reperfusion
will be characterized. The specific aims are to: 1) Determine the phenotypic
differences of isolated hearts and coronary vessels from the parental strains
by studying the responses to: ischemia alone and adaptation to intermittent
hypoxia prior to ischemia; 2) Map the gene(s) responsible for adaption in
intermittent hypoxia and susceptibility to myocardial ischemia using a total
genome scan approach; 3) Develop congenic strains in response to: ischemia
alone and adaptation to intermittent hypoxia prior to ischemia; and 4) Use
microarray technology to study the expression of genes within the heart
adapted to intermittent hypoxia. This project may provide detailed
information regarding the genetic basis for adaption to intermittent hypoxia
and susceptibility to myocardial ischemia in a genetic model system, which may
prove useful for detailed physiological, biochemical and pharmacological
assessment.
总的目标是定位基因(S)负责
对间歇性缺氧引起的心肌缺血的易感性,
在一个新的模型系统中表征生理学。 患者
阻塞性睡眠呼吸暂停具有增加的心血管发病率,
mortality. 高血压、高血脂、糖尿病等疾病
糖尿病具有潜在的遗传基础,并代表以下疾病的风险因素:
缺血性心脏病 然而,遗传成分(S)的基础
间歇性低氧对心肌缺血易感性影响
未知 据推测,遗传因素是负责
对间歇性缺氧引起的心肌缺血的敏感性增加
Dahl S大鼠与Brown Norway大鼠相比。 这一假设将是
用达尔鼠穿越布朗挪威进行测试。 离体心脏模型
和冠状动脉血管将被用于促进离散的,良好控制的
对缺血的易感性的研究,
间歇性缺氧 将进行全基因组扫描,
间歇性低氧适应的数量性状基因座
和对心肌缺血的易感性。 表型差异
缺血和再灌注导致的母体和同类衍生物
将被定性。 具体目标是:1)确定表型
离体心脏和冠状血管与亲本株的差异
通过研究对缺血的反应:单独缺血和间歇性适应
2)定位负责缺血前适应的基因;
间歇性缺氧与心肌缺血易感性的关系
基因组扫描方法; 3)开发同类菌株以响应:缺血
单独使用和在缺血前适应间歇性缺氧;和4)使用
微阵列技术研究心脏内基因的表达
适应间歇性缺氧 该项目可以提供详细的
关于适应间歇性缺氧的遗传基础的信息
和对心肌缺血的易感性,这可能
证明对详细的生理、生物化学和药理学有用
考核
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)
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