Corticosteroid hormone action in cardiomyocytes - impact on heart failure

肾上腺是一个激素产生器官，分泌两个主要类别的类固醇激素，皮质醇和醛固酮。皮质醇通过与其受体结合，在机体内调节能量平衡、免疫功能、炎症反应和应激反应等方面发挥着重要作用。相比之下，醛固酮通过与相关受体结合来调节盐稳态和血压。除了这些作用，许多研究已经确定，醛固酮对心脏和血管表现出有害作用，可能导致心脏病患者的心力衰竭。反之亦然，用抑制醛固酮的药物进行医学治疗导致患有心力衰竭的患者的存活率提高。本研究旨在探讨醛固酮和皮质醇对心肌细胞的作用，以阐明其在心脏疾病发生、发展中的分子机制。研究将主要基于实验室内使用心脏细胞系和从大鼠心脏生长的心脏细胞，但也将涉及直接分析接受心脏手术的患者的心脏活检材料。对这些机制的更好理解将最终导致心力衰竭治疗的新治疗策略。

The adrenal gland is a hormone producing organ that secretes two principal classes of steroid hormones, cortisol and aldosterone. Cortisol through binding to its receptor plays a vitally important role in the body by regulating energy homeostasis, immune function, inflammation and stress response. By contrast, aldosterone by binding to a related receptor regulates salt homeostasis and blood pressure. Besides these effects, many studies have now established that aldosterone exhibits deleterious effects on the heart and blood vessels that may contribute to heart failure in patients with heart disease. Vice versa, medical treatment with drugs that inhibit aldosterone lead to improved survival of patients suffering from heart failure. Cortisol by contrast, seems to play a protective role but the underlying mechanisms are unknown.Our study aims to determine the specific effects of aldosterone and cortisol on heart muscle cells to clarify the underlying molecular mechanisms that are involved in the development and progression of cardiac disease. Studies will be largely based within the laboratory using cardiac cell lines and heart cells grown from rat heart but will also involve the direct analysis of heart biopsy material from patients undergoing cardiac surgery. A better understanding of these mechanisms will ultimately result in new therapeutic strategies in the treatment of heart failure.