A transgenic mouse model for studying the role of human chymase in regulating tissue angiotensin II formation

研究人食糜酶在调节组织血管紧张素 II 形成中的作用的转基因小鼠模型

• 批准号: nhmrc : 109001
• 负责人: Prof Ahsan Husain
• 金额: $ 35.74万
• 依托单位: Victor Chang Cardiac Research Institute
• 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/transgenic-mouse-model-ii-formation/77547
• 关键词: transgenic; mouse; model; studying; role

Cardiac hypertrophy or heart enlargement is an important risk factor in the eventual development of heart failure. It is now well known that heart enlargement can be produced by pressure overload of hypertension and-or by increased hormonal inputs directly to the heart. Angiotensin II, a hormone that produces hypertension and heart enlargement, was previously thought only to be produced by the enzyme ACE. Although ACE inhibitors are widely used in treatment of hypertension and heart failure several studies now show that ACE inhibition only partially reduces angiotensin II levels in humans. Our recent studies suggest that the novel enzyme human chymase may be involved in regulating angiotensin II levels in human tissues including the heart and blood vessels. By introducing a gene for human chymase in mice we plan to create a mouse model that allows us to understand the importance of human chymase in cardiovascular physiology and disease. This mouse model would not only show the involvement of human chymase in regulating heart and vessel angiotensin II levels and in the development of hypertension and heart enlargement but also will provide an animal model essential for the development of human chymase inhibitors.

心脏肥大或心脏增大是最终发展为心力衰竭的重要危险因素。现在大家都知道，心脏增大可能是由高血压压力过大和或直接输入心脏的激素增加引起的。血管紧张素II，一种导致高血压和心脏增大的激素，以前被认为只由ACE酶产生。尽管ACE抑制剂被广泛用于治疗高血压和心力衰竭，但一些研究表明，ACE抑制只能部分降低人类血管紧张素II水平。我们最近的研究表明，新的酶人乳糜酶可能参与调节血管紧张素II水平在人体组织，包括心脏和血管。通过在小鼠中引入人类乳糜酶基因，我们计划创建一个小鼠模型，使我们能够了解人类乳糜酶在心血管生理学和疾病中的重要性。该小鼠模型不仅表明人乳糜酶参与调节心脏和血管紧张素II水平以及高血压和心脏增大的发生，而且为开发人乳糜酶抑制剂提供了必要的动物模型。