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

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，每年夺去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，并且发病率继续增加。最近的两项大规模临床试验表明，当盐皮质激素受体（MR）阻滞剂被纳入心力衰竭或心脏病发作后的当前最佳实践治疗时，患者结局改善30-35%。这些益处背后的机制仍有待确定。我们已经表明，激素醛固酮及其受体，MR，不仅在高血压的发展中发挥重要作用，而且心脏疾病的进展。我们最近的研究表明，阻断MR不仅可以预防心脏纤维化和血管损伤，还可以逆转这一过程。为了理解MR信号传导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具有MR基因失活的小鼠。通过这种方式，我们可以识别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以使MR的心脏特异性阻断剂的开发具有最小的副作用（如果有的话）。

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.