Primary cardiac hypertrophy - a functional genetic approach to investigate cellular mechanisms of metabolic remodelling

原发性心脏肥大——一种研究代谢重塑细胞机制的功能遗传学方法

• 批准号: nhmrc : 114167
• 负责人: Prof Leanne Delbridge
• 金额: $ 15.12万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/primary-cardiac-hypertrophy-metabolic-remodelling/78352
• 关键词: Primary; cardiac; hypertrophy; functional; genetic

Population studies have recently shown that enlargement of the heart, even when blood pressure is normal, is a risk factor which can lead to cardiovascular complications. Very little is known about the alterations in heart cell structure and function which occur in cardiac enlargement not complicated by high blood pressure. It is possible that specific metabolic abnormalities underlie this condition. The goal of this study is to use a newly developed genetically manipulated experimental animal model to study the function of single heart cells. In this model one of the glucose transporters has been deleted. Our goal is to compare heart function in this genetic model with heart function in diabetes. Cells are isolated from hearts using enzyme treatments and investigated microscopically to determine if there are subcellular structural alterations. Functional studies are performed on individual viable cells using a combination of electrical recording techniques and fluorescence imaging methods. The experimental aim is to assess whether there is disruption of sodium, calcium or pH regulation associated with cardiac enlargement associated with metabolic abnormalities. This research will assist in identifying appropriate therapeutic strategies for intervention in the treatment or prevention of conditions associated with cardiac enlargement.

最近的人口研究表明，即使血压正常，心脏增大也是导致心血管并发症的危险因素。对于未并发高血压的心脏扩大时发生的心脏细胞结构和功能的改变知之甚少。这种情况可能是由特定的代谢异常引起的。这项研究的目标是利用新开发的基因操纵实验动物模型来研究单个心脏细胞的功能。在该模型中，其中一个葡萄糖转运蛋白已被删除。我们的目标是将这种遗传模型中的心脏功能与糖尿病中的心脏功能进行比较。使用酶处理从心脏中分离细胞，并在显微镜下进行研究以确定是否存在亚细胞结构改变。结合电记录技术和荧光成像方法对单个活细胞进行功能研究。实验目的是评估是否存在与代谢异常相关的心脏扩大相关的钠、钙或 pH 调节的破坏。这项研究将有助于确定适当的治疗策略，以干预或预防与心脏扩大相关的疾病。