Aldosterone Dysfunction and Mineralocorticoid Pathway Activation in Resistant and Severe Hypertension

Resistant and severe hypertension represent a growing global health burden and are associated with a markedly increased risk of cardiovascular, renal, and metabolic complications. Despite the availability of multiple antihypertensive therapies, a substantial proportion of patients remain inadequately controlled, highlighting important gaps in current pathophysiological understanding and clinical management. Increasing evidence indicates that aldosterone excess and dysregulated mineralocorticoid receptor (MR) signaling play central roles in driving treatment resistance, vascular dysfunction, cardiac remodeling, and cardiometabolic disease. Primary aldosteronism and related aldosterone-driven phenotypes are now recognized to be substantially more prevalent than previously appreciated across the spectrum of hypertension. At the same time, advances in adrenal biology—including the discovery of somatic mutations in aldosterone-producing adenomas, improved characterization of adrenal steroidogenesis, and the emergence of multi-omics and single-cell technologies—are reshaping our understanding of the mechanisms underlying aldosterone dysregulation. These developments provide new opportunities to refine disease classification, identify novel biomarkers, and develop targeted therapeutic strategies. However, significant challenges remain. Aldosterone-related mechanisms are frequently underdiagnosed in clinical practice, diagnostic pathways continue to evolve, and the integration of molecular insights into cardiovascular risk prediction and personalized treatment is still limited. Bridging this gap between mechanistic discovery and clinical application is essential for improving outcomes in patients with resistant and severe hypertension. This Research Topic aims to advance understanding of aldosterone dysfunction and MR pathway activation across the continuum of hypertension. We particularly encourage studies that integrate adrenal pathophysiology with cardiovascular and metabolic outcomes, and that leverage emerging technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, spatial biology and single-cell approaches to uncover new mechanisms and therapeutic targets. We welcome original research articles, reviews, mini-reviews, and perspectives addressing, but not limited to, the following themes: • Mechanisms of aldosterone excess and MR activation in resistant and severe hypertension• Adrenal biology and molecular determinants of aldosterone production • Primary aldosteronism, subclinical hyperaldosteronism, and evolving diagnostic paradigms• Aldosterone–renin profiling, ARR interpretation, and biomarker discovery• Multi-omics and systems biology approaches in aldosterone-driven hypertension• Genetic and epigenetic regulation of mineralocorticoid signaling• MR-mediated vascular dysfunction, inflammation, fibrosis, and cardiac remodeling• Interactions between renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system activation, immune pathways, and metabolism• Aldosterone in obesity-related and cardiometabolic hypertension• Cardiovascular outcomes and risk stratification in aldosterone-driven disease• Emerging therapeutic strategies including MR antagonists and targeted endocrine interventions• Precision medicine and individualized approaches to resistant hypertensionBy integrating advances in adrenal endocrinology, cardiovascular research, and systems biology, this Research Topic aims to improve recognition of aldosterone-driven disease and facilitate the translation of mechanistic insights into clinical practice. Ultimately, this collection seeks to support the development of more precise, mechanism-based approaches for diagnosing and managing resistant and severe hypertension. Topic editors: Nicolas Renna, Elena Aisha Azizan, Vin-Cent Wu Source: https://www.frontiersin.org/research-topics/79857/aldosterone-dysfunction-and-mineralocorticoid-pathway-activation-in-resistant-and-severe-hypertension