Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess

Tapia-Castillo, Alejandra; Carvajal, Cristián A.; Pérez, J.A. Hermida; Fardella, Carlos E.

doi:10.1007/s12020-022-03103-x

Cited by 4 publications

(5 citation statements)

References 57 publications

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“…Because high glucocorticoid levels can also activate the MR, it is worth mentioning that some of the effects described could occur through this receptor (58). This hypothesis is supported by a recent study that reported that hypertensive patients diagnosed with non-classic apparent mineralocorticoid excess plus PA presented higher NGAL plasma levels than those with PA only (59). The regulation of NGAL by the glucocorticoid-MR complex in other immune cell types in endocrine AH remains to be explored further.…”

Section: Ngal and Endocrine Arterial Hypertensionmentioning

confidence: 69%

Neutrophil gelatinase–associated lipocalin as an immunomodulator in endocrine hypertension

Araos

Amador

2022

Front. Endocrinol.

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In recent studies, primary aldosteronism (PA) has been reported as the most common etiology for secondary hypertension of endocrine origin, accounting for approximately 10% of cases. In PA, excess aldosterone production can lead to deleterious effects at the cardiovascular (CV) and renal levels by activating mineralocorticoid receptors, which involves an increase in pro-inflammatory and pro-fibrotic mediators. Among these mediators, neutrophil gelatinase–associated lipocalin (NGAL), a secretion glycoprotein belonging to the lipocalin superfamily, has been closely linked to CV and renal damage in several pathological conditions. Because NGAL can be detected in biofluids such as plasma and urine, it has been proposed as a damage biomarker for target tissues and has also been studied for its role in hypertension and associated with PA. NGAL is produced by many different cell types, can be carried on extracellular vesicles, and is modulated by microRNAs, which would support its use as a biomarker for endocrine hypertension due to PA. Over the last decade, studies have shown that NGAL is necessary for the development of aldosterone-induced hypertension and that is associated with end-organ damage. In addition, it has been proposed that some mechanisms are dependent on the activation of immune cells, such as dendritic cells and macrophages, where the release of specific cytokines (i.e., interleukin [IL]-23) or chemokines (i.e., CCL-5) induced by aldosterone would depend on NGAL. Subsequently, this activates the T helper (Th) lymphocytes, such as Th17 and Th2, resulting in CV and renal fibrosis due to the high aldosterone levels. Although the immune system has been closely associated with essential hypertension, its participation in endocrine hypertension has not been fully elucidated. This review discusses the link between NGAL and endocrine hypertension, particularly in the context of PA, and their possible regulators and mechanisms, with a focus on its role as an immunomodulator.

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Section: Ngal and Endocrine Arterial Hypertensionmentioning

confidence: 69%

Neutrophil gelatinase–associated lipocalin as an immunomodulator in endocrine hypertension

Araos

Amador

2022

Front. Endocrinol.

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“…In particular, Neutrophil Gelatinase-Associated Lipocain (NGAL), a quite recent and emergent molecule involved in acute kidney injury (AKI) and measured in uEVs, could be potentially evaluated ( 34 ). NGAL was recently observed to be involved in MR induced cardiovascular damage, but its role in PA pathophysiology is still not clear, thus we plan to evaluate it in further studies ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism

et al. 2023

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BackgroundUrinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information “in vivo” without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).MethodsPatients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.ResultsMS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH vs PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH vs PA, as well as A1AG1 (AGP1).ConclusionThrough this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH.

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“…Besides lipids and proteins, uEVs also carry RNA molecules and are secreted from renal epithelial cells into the urine, thus providing access to information about kidney tissue physiology and possibly to kidney-related diseases pathophysiology ( 21 , 22 ). Most studies, however, have focused, on the proteins and non-coding RNA profiles of uEVs and almost all are related to endocrine hypertension referring more specifically to primary aldosteronism (PA) and to apparent mineralocorticoid excess (AME) ( 12 – 14 , 16 , 17 , 19 , 20 , 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…Despite the high interest on uEVs transcriptome, most reports on uEVs rely almost exclusively on noncoding RNA, namely miRNA ( 14 ), with only few studies focusing on the analysis of mRNA transcripts ( 6 , 28 ). This is due, at least in part, to the complexity of obtaining mRNA that may be adequate in terms of integrity and quantity for transcriptomic studies, since mRNA is usually present in very exiguous amount in uEVs in comparison to more abundant molecules (i.e., proteins and noncoding RNAs).…”

Section: Discussionmentioning

confidence: 99%

“…The defective enzyme activity that characterizes the disease is defined by low renin hypertension due to an excessive MR activation by cortisol. In recent years a milder form of the disease due to partial 11b-HSD2 deficiency was also described, which has been termed nonclassical AME (NCAME) and in which analysis of uEVs loading has revealed a possible role of several noncoding RNAs (12)(13)(14).…”

Section: Hsd11b2 Gene Expression In Apparent Mineralocorticoid Excess...mentioning

confidence: 99%

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Urinary extracellular vesicles carry valuable hints through mRNA for the understanding of endocrine hypertension

et al. 2023

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Urinary extracellular vesicles (uEVs), released from cells of the urogenital tract organs, carry precious information about originating tissues. The study of molecules transported through uEVs such as proteins, lipids and nucleic acids provides a deeper understanding of the function of the kidney, an organ involved in the pathogenesis of hypertension and a target of hypertension-mediated organ damage. Molecules derived from uEVs are often proposed for the study of disease pathophysiology or as possible disease diagnostic and prognostic biomarkers. Analysis of mRNA loading within uEVs may be a unique and readily obtainable way to assess gene expression patterns of renal cells, otherwise achievable only by an invasive biopsy procedure. Interestingly, the only few studies investigating transcriptomics of hypertension-related genes through the analysis of mRNA from uEVs are inherent to mineralocorticoid hypertension. More specifically, it has been observed that perturbation in human endocrine signalling through mineralcorticoid receptors (MR) activation parallels changes of mRNA transcripts in urine supernatant. Furthermore, an increased copy number of uEVs-extracted mRNA transcripts of the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene were detected among subjects affected by apparent mineralocorticoid excess (AME), a hypertension-inducing autosomal recessive disorder due to a defective enzyme function. Moreover, by studying uEVs mRNA, it was observed that the renal sodium chloride cotransporter (NCC) gene expression is modulated under different conditions related to hypertension. Following this perspective, we illustrate here the state of the art and the possible future of uEVs transcriptomics towards a deeper knowledge of hypertension pathophysiology and ultimately more tailored investigational, diagnostic-prognostic approaches.

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Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess

Cited by 4 publications

References 57 publications

Neutrophil gelatinase–associated lipocalin as an immunomodulator in endocrine hypertension

Neutrophil gelatinase–associated lipocalin as an immunomodulator in endocrine hypertension

Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism

Urinary extracellular vesicles carry valuable hints through mRNA for the understanding of endocrine hypertension

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