Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
Curr Opin Endocrinol Diabetes Obes. 2013 Jun;20(3):198-203. doi: 10.1097/MED.0b013e328360c200.
Aldosterone is now recognized as an increasingly important contributor to cardiometabolic pathology via inflammatory and fibrosis-related pathways in addition to its classically described role in sodium and volume regulation. Consequently, much effort has been directed towards characterizing the molecular pathways involved in aldosterone-mediated fibrosis and inflammation. What was once viewed as straightforward steroid hormone biology is now appreciated as a highly complex and tightly regulated series of pathways and interactions. These recognitions have fuelled a multidisciplinary effort to identify precisely how aldosterone mediates intracellular activation of both genomic (latent) and nongenomic (rapid) mechanisms of influence. This review will explore recent novel pathways regulating aldosterone action, focusing on the nongenomic pathways.
Several recent discoveries have redefined our understanding of aldosterone interactions at the cellular level. This includes activation of the mineralocorticoid receptor at the plasma membrane instead of via classical nuclear hormone receptor interaction, and identification of novel cofactor scaffolding proteins that modify aldosterone influence at the cellular level. In addition, aldosterone activation of secondary messenger system cascades can occur directly and independent of mineralocorticoid receptor interaction.
Substantial progress in detailing the molecular biology of aldosterone regulation and action should facilitate study of how it exerts detrimental effects in cardiometabolic diseases. However, to date, the clinical impact of these discoveries has not been validated. Translational efforts are now required to determine if novel therapeutic targets can be developed.
醛固酮除了在经典的钠和容量调节中发挥作用外，现在还被认为通过炎症和纤维化相关途径对心脏代谢病理学有越来越重要的影响。因此，人们已经投入了大量的努力来描述醛固酮介导的纤维化和炎症相关的分子途径。曾经被认为是简单的甾体激素生物学，现在被认为是一个高度复杂和严格调控的途径和相互作用系列。这些认识促使多学科努力准确地确定醛固酮如何介导细胞内基因组（潜在）和非基因组（快速）影响的激活。这篇综述将探讨最近调节醛固酮作用的新途径，重点是非基因组途径。
最近的一些发现重新定义了我们对醛固酮在细胞水平上相互作用的理解。这包括在细胞膜上而不是通过经典的核激素受体相互作用激活盐皮质激素受体，以及鉴定新的辅助因子支架蛋白，这些蛋白可以在细胞水平上改变醛固酮的影响。此外，醛固酮对第二信使系统级联的激活可以直接发生，而不依赖于盐皮质激素受体的相互作用。
详细描述醛固酮调节和作用的分子生物学的进展应该有助于研究它在心脏代谢疾病中产生有害影响的机制。然而，到目前为止，这些发现的临床影响尚未得到验证。现在需要进行转化研究，以确定是否可以开发新的治疗靶点。
