Alfarano Maria, Marchionni Giulia, Costantino Jacopo, Ballatore Federico, Verardo Romina, Miraldi Fabio, Ciciarello Francesco Luigi, Petramala Luigi, Letizia Claudio, Frustaci Andrea, Chimenti Cristina
Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Policlinico San Matteo Pavia IRCCS Foundation, University of Pavia, Pavia, Italy.
JACC Adv. 2025 May 3;4(6 Pt 1):101762. doi: 10.1016/j.jacadv.2025.101762.
High levels of aldosterone are associated with vascular and cardiac remodeling, myocardial fibrosis, and endothelial dysfunction with consequent increased risk of cardiovascular events and cardiovascular mortality. Indeed, mineralcorticoid receptor antagonists (MRAs) are recommended in the treatment of arterial hypertension, heart failure, alone or associated with chronic kidney disease. Nevertheless, molecular pathways underlying aldosterone-induced cardiac remodeling are poorly investigated. High levels of aldosterone induce reactive oxygen species with consequent oxidative stress and mitochondrial dysfunction. Moreover, aldosterone induces myocardial hypertrophy through increase of sarcomere mass mediated by pro-hypertrophic effect mediated by a G protein-coupled receptor kinase 5 cytosolic signaling and retention of ions and water regulated by aquaporins. Aim of this review is to report the data from the literature regarding excessive aldosterone signaling in mediating cardiovascular disease, also highlighting the morphostructural and molecular pathways correlated to myocardial damage and the role of MRAs in clinical practice.
高水平的醛固酮与血管和心脏重塑、心肌纤维化以及内皮功能障碍相关,从而增加心血管事件和心血管死亡率的风险。事实上,盐皮质激素受体拮抗剂(MRAs)被推荐用于治疗动脉高血压、心力衰竭,单独使用或与慢性肾脏病联合使用。然而,醛固酮诱导心脏重塑的分子途径研究较少。高水平的醛固酮会诱导活性氧的产生,从而导致氧化应激和线粒体功能障碍。此外,醛固酮通过由G蛋白偶联受体激酶5胞质信号介导的促肥大效应增加肌节质量以及由水通道蛋白调节的离子和水的潴留来诱导心肌肥大。本综述的目的是报告文献中关于醛固酮信号过度介导心血管疾病的数据,同时强调与心肌损伤相关的形态结构和分子途径以及MRAs在临床实践中的作用。