Urinary Exosomes and Their Cargo: Potential Biomarkers for Mineralocorticoid Arterial Hypertension?

Abstract

Arterial hypertension (AHT) currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases. Excess of aldosterone or cortisol increases the activity of the mineralocorticoid receptor (MR) in epithelial and non-epithelial cells. Current research in this field highlights the potential regulatory mechanisms of the MR pathway, including pre-receptor regulation of the MR (action of 11BHSD2), MR activating proteins, and the downstream genes/proteins sensitive to MR (e.g., epithelial sodium channel, NCC, NKCC2). Mineralocorticoid AHT is present in 15–20% of hypertensive subjects, but the mechanisms associated to this condition have been poorly described, due mainly to the absence of reliable biomarkers. In this way, steroids, peptides, and lately urinary exosomes are thought to be potential reporters of biological processes. This review highlight exosomes and their cargo as potential biomarkers of metabolic changes associated to mineralocorticoid AHT. Recent reports have shown the presence of RNA, microRNAs, and proteins in urinary exosomes, which could be used as biomarkers in physiological and pathophysiological conditions. However, more studies are needed in order to benefit from exosomes and the exosomal cargo as a diagnostic tool in mineralocorticoid AHT.

Determination of variability due to biological and technical variation in urinary extracellular vesicles as a crucial step in biomarker discovery studies

“…Extracellular vesicles (EVs) play a role in intercellular communication under physiological and pathophysiological conditions [1,2]. Urinary EVs originate from cells lining the nephron lumen and the urinary tract and from potentially present acute injured sites [3,4]. The cargo of EVs is thought to reflect the cell‐type of origin [4–6].…”

“…Urinary EVs originate from cells lining the nephron lumen and the urinary tract and from potentially present acute injured sites [3,4]. The cargo of EVs is thought to reflect the cell‐type of origin [4–6]. In this way, exploring the urinary EV cargo can lead to biomarkers for the diagnosis or prediction of progression of urological diseases [5].…”

Atomic Force Microscopy Based Tip-Enhanced Raman Spectroscopy in Biology

“…AFM-TERS can also be used to characterize amyloid fibrils, which can be helpful to seek for the reasons of various neurodegenerative diseases [ 25 ]. Furthermore, biomarkers are biochemical indexes which can be used to measure and evaluate the specific features in biological processes, pathogenic processes, and management processes [ 100 , 101 , 102 ]. Detecting diagnostic markers can help to the identification, diagnosis, remedy and prevention of diseases because it can mark the changes in the structures and functions of organs, tissues, and cells.…”

Detection of Urinary Exosomal HSD11B2 mRNA Expression: A Useful Novel Tool for the Diagnostic Approach of Dysfunctional 11β-HSD2-Related Hypertension

“…Fourteen members of a family previously studied for a story of AME syndrome ( 14 ) were enrolled for this study. The subjects were subdivided according to their HSD11B2 662 C>G genotype (homozygous, 662 GG; heterozygous, 662 AG; wild type, 662 AA) and phenotype [normotensive (N); hypertensive (H)].…”

“…HSD11B2 mRNA is expected to be present in urinary exosomes, considering the tubular localization of the enzyme; however, its presence in exosomes has not been documented so far. Some authors hypothesized the usefulness of detecting HSD11B2 or even other exosomal mRNAs for the study of the pathophysiological mechanisms of hypertensive diseases and in particular for the diagnosis of mineralocorticoid hypertension ( 14 ). Urinary exosomes are considered extremely valuable for diagnostic purposes as they are considered as kidney liquid biopsies ( 15 ) because urinary EVs (uEVs) are mainly derived from renal cells while circulating serum EVs, under physiological conditions, cannot cross the nephron barrier ( 12 , 16 ).…”