Role of Mineralocorticoid Receptors in Cardiovascular Disease

Mineralocorticoid receptor (MR) antagonists (MRAs) are first-line therapy for primary aldosteronism and guideline-recommended treatment for heart failure (HF). The cardiovascular benefits of MRAs exceed blood pressure reduction, reflecting inhibition of inappropriate MR activation in cardiac and vascular tissues, and immune cells. Early preclinical studies demonstrated that aldosterone excess induces myocardial inflammation and fibrosis through MR-dependent pathways, and clinical trials established the efficacy of MRAs in reducing morbidity and mortality in HF. Nonsteroidal MRAs are now available, and aldosterone synthase inhibitors have commenced clinical testing; it is thus timely to revisit the mechanisms of MR activation in the heart and related cell types. This review will discuss key findings from preclinical and clinical studies of MRA use in HF and mineralocorticoid infusion, and update our understanding of MR actions in the normal myocardium and in the pathophysiology of primary aldosteronism and HF. Emerging data on aldosterone-mediated cardiovascular injury in patients with primary aldosteronism, including structural and functional cardiac changes and links to adverse outcomes, will be included, along with recent advances in MR-targeted pharmacology that offer improved selectivity and safety profiles. This review provides an updated understanding of MR-dependent pathways in the cardiovascular system and potential strategies for optimizing cardiovascular protection in both primary aldosteronism and HF.