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，也是澳大利亚死亡和残疾的主要原因，每年夺去50 000多名澳大利亚人的生命。这些死亡中有许多是心力衰竭造成的，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，当矿皮质激素受体（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治疗中时，患者预后可改善30-35%。这些益处背后的机制仍有待确定。我们已经证明醛固酮激素及其受体，MR，不仅在高血压的发展中发挥重要作用，而且在心脏病的发展中也起着重要作用。我们最近的研究表明，阻断MR不仅可以防止心脏纤维化和血管损伤，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MR基因仅在特定细胞中失活的小鼠。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，并将我们的研究重点放在这些细胞类型上。了解核磁共振的细胞特异性调节机制可能有助于开发具有最小副作用的心脏特异性核磁共振阻滞剂。

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.