Transcriptomics, Epigenetics, and Metabolomics of Primary Aldosteronism

Abstract

Introduction: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, mainly caused by aldosterone-producing adenomas or hyperplasia; understanding its pathophysiological background is important in order to provide ameliorative treatment strategies. Over the past several years, significant progress has been documented in this field, in particular in the clarification of the genetic and molecular mechanisms responsible for the pathogenesis of aldosterone-producing adenomas (APAs). Methods: Systematic searches of the PubMed and Cochrane databases were performed for all human studies applying transcriptomic, epigenetic or metabolomic analyses to PA subjects. Studies involving serial analysis of gene expression and microarray, epigenetic studies with methylome analyses and micro-RNA expression profiles, and metabolomic studies focused on improving understanding of the regulation of autonomous aldosterone production in PA were all included. Results: In this review we summarize the main findings in this area and analyze the interplay between primary aldosteronism and several signaling pathways with differential regulation of the RNA and protein expression of several factors involved in, among others, steroidogenesis, calcium signaling, and nuclear, membrane and G-coupled protein receptors. Distinct transcriptomic and metabolomic patterns are also presented herein, depending on the mutational status of APAs. In particular, two partially opposite transcriptional and steroidogenic profiles appear to distinguish APAs carrying a KCNJ5 mutation from all other APAs, which carry different mutations. Conclusions: These findings can substantially contribute to the development of personalized treatment in patients with PA.

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

“…As the terminal of an organism’s biological process, an altered metabolism is one of the hallmarks of noxious effects in the heart, where changes in protein expression and injures in cardiac function ultimately lead to aberrant cellular metabolism ( Kroemer et al, 2018 ; Luz and Tokar, 2018 ). Fortunately, the emergence of metabolomics research has provided a new approach to statistically and quantitatively visualizing evidence according to the dynamic information in overall profiles of endogenous metabolites after the biological system has suffered from exogenous disturbance and stimulation ( Al-Ansari et al, 2021 ; Shibutami and Takebayashi, 2021 ; Spyroglou et al, 2021 ). Indeed, a burst of research utilizing untargeted metabolomics technology has been published in the field of cardiac toxicology over the past decades, based on the dual advantages of global material scanning and the accuracy of material annotation, and contributing to numerous methodological advances in interpreting the enrolled metabolic pathway and toxic mechanism ( Parry et al, 2018 ; Palmer et al, 2020 ).…”

Serum Metabolomic Patterns in Patients With Aldosterone-Producing Adenoma

“…Early studies on PA metabolomics mainly focused on steroid profiling, which indicated elevated 18-hydroxycortisol and 18oxocortisol levels in APA patients (Spyroglou et al, 2021). Recently, Alessandro Lana et al performed metabolic profiling to distinguish between EHT and APA patients and between APA and bilateral adrenal hyperplasia (BAH) patients.…”

“…In recent decades, much effort has been exerted to improve our understanding of PA. Metabolomics, a high-throughput approach, has been adopted to describe the metabolic features of PA using tumor or urinary samples from APA patients to reveal the characteristics or improve the diagnosis of PA (Spyroglou et al, 2021). However, serum is an ideal sample for disease diagnosis, disease monitoring, and mechanistic investigations and not only reflects the changes at the genomic and proteomic levels but also is influenced by environmental factors (Hashim et al, 2019).…”

Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation

“…Below we focus on differentially expressed genes in APAs which are implicated in mechanisms of cell death and proliferation. The application of transcriptomics to identify mechanisms of aldosterone overproduction are described elsewhere ( 66 , 67 ).…”