Cellular Localisation of mineralocorticoid receptor-mediated vascular inflammation and cardiac fibrosis.

盐皮质激素受体介导的血管炎症和心脏纤维化的细胞定位。

• 批准号: nhmrc : 388914
• 负责人: Dr Morag Young
• 金额: $ 31.76万
• 依托单位: Prince Henry's Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cellular-localisation-mineralocorticoid-cardiac-fibrosis/94807
• 关键词: Cellular; Localisation; mineralocorticoid; receptor; mediated

Cardiovascular disease is a major health and economic burden throughout the world, especially in developed countries and is the leading cause of death and disability in Australia, claiming the lives of over 50,000 Australians each year. Heart failure accounts for many of these deaths and the incidence continues to increase. Two recent large scale clinical trials have shown a 30-35% improvement in patient outcome when a blocker for the mineralocorticoid receptor (MR) is included in current best practice therapy for either heart failure or after a heart attack. The mechanisms underlying these benefits remain to be identified. We have shown that the hormone aldosterone and its receptor, the MR, not only play an important role in the development of high blood pressure but also the progression of cardiac disease. Our most recent studies have shown that blocking the MR not only prevents cardiac fibrosis and vascular damage, but also reverses this process. To understand the mechanisms that translate MR signalling into blood vessel damage and cardiac fibrosis we wish to use mice who have the MR gene inactivated in specific cells only. In this way we can identify those cells critical to the disease process and focus our investigations to these cell types. Understanding the cell specific regulatory mechanisms for the MR may enable the development of heart-specfic blockers of the MR that have minimal, if any side effects.

心血管疾病是全世界，特别是发达国家的主要健康和经济负担，是澳大利亚死亡和残疾的主要原因，每年夺走5万多澳大利亚人的生命。心力衰竭是这些死亡中的许多原因，而且发病率还在继续增加。最近的两项大规模临床试验表明，当盐皮质激素受体(MR)阻滞剂被纳入目前治疗心力衰竭或心脏病发作后的最佳实践疗法时，患者预后改善了30%-35%。这些好处背后的机制仍有待确定。我们已经证明，激素醛固酮及其受体MR不仅在高血压的发生发展中起重要作用，而且在心脏病的进展中也起着重要作用。我们最新的研究表明，阻断MR不仅可以预防心脏纤维化和血管损伤，而且还可以逆转这一过程。为了理解将MR信号转化为血管损伤和心脏纤维化的机制，我们希望使用仅在特定细胞中使MR基因失活的小鼠。通过这种方式，我们可以识别那些对疾病过程至关重要的细胞，并将我们的研究集中在这些细胞类型上。了解MR的细胞特异性调节机制可能使心脏特异性MR阻滞剂的开发具有最小的副作用(如果有的话)。