Urinary Proteomics Reveals Key Markers of Salt Sensitivity in Hypertensive Patients During Saline Infusion

Overview

Journal J Nephrol

Publisher Springer

Specialty Nephrology

Date 2021 Jan 5

PMID 33398797

Citations 5

Authors

Vittoria Matafora

Chiara Lanzani

Laura Zagato

Paolo Manunta

Miriam Zacchia

Francesco Trepiccione

Marco Simonini

Giovambattista Capasso

Angela Bachi

Affiliations

Soon will be listed here.

Abstract

Background: Hypertension is a complex disease and is the major cause of cardiovascular complications. In the vast majority of individuals, the aetiology of elevated blood pressure (BP) cannot be determined, thus impairing optimized therapies and prognosis for individual patients. A more precise understanding of the molecular pathogenesis of hypertension remains a pressing priority for both basic and translational research. Here we investigated the effect of salt on naive hypertensive patients in order to better understand the salt intake-blood pressure relationship.

Methods: Patients underwent an acute saline infusion and were defined as salt-sensitive or salt-resistant according to mean blood pressure changes. Urinary proteome changes during the salt load test were analysed by a label-free quantitative proteomics approach.

Results: Our data show that salt-sensitive patients display equal sodium reabsorption as salt-resistant patients, as major sodium transporters show the same behaviour during the salt load. However, salt-sensitive patients regulate the renin angiotensin system (RAS) differently from salt-resistant patients, and upregulate proteins, as epidermal growth factor (EGF) and plasminogen activator, urokinase (PLAU), involved in the regulation of epithelial sodium channel ENaC activity.

Conclusions: Salt-sensitive and salt-resistant subjects have similar response to a saline/volume infusion as detected by urinary proteome. However, we identified glutamyl aminopeptidase (ENPEP), PLAU, EGF and Xaa-Pro aminopeptidase 2 precursor XPNPEP2 as key molecules of salt-sensitivity, through modulation of ENaC-dependent sodium reabsorption along the distal tubule.

Citing Articles

Multi-omics Investigations in Endocrine Systems and Their Clinical Implications.

Peliciari-Garcia R, de Barros C, Secio-Silva A, de Barros Peruchetti D, Romano R, Bargi-Souza P Adv Exp Med Biol. 2024; 1443:187-209.

PMID: 38409422 DOI: 10.1007/978-3-031-50624-6_10.

Kidney and blood pressure regulation-latest evidence for molecular mechanisms.

Suzumoto Y, Zucaro L, Iervolino A, Capasso G Clin Kidney J. 2023; 16(6):952-964.

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Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?.

Ledeganck K, Van Eyck A, Wouters K, Vermeiren E, De Winter B, Verhulst S PLoS One. 2023; 18(3):e0283716.

PMID: 36996194 PMC: 10062545. DOI: 10.1371/journal.pone.0283716.

Decoding the mechanism of hypertension through multiomics profiling.

Adua E J Hum Hypertens. 2022; 37(4):253-264.

PMID: 36329155 PMC: 10063442. DOI: 10.1038/s41371-022-00769-8.

Urinary Proteomic Characteristics of Hyperuricemia and Their Possible Links with the Occurrence of Its Concomitant Diseases.

Huo S, Wang H, Yan M, Xu P, Song T, Li C ACS Omega. 2021; 6(14):9500-9508.

PMID: 33869930 PMC: 8047722. DOI: 10.1021/acsomega.0c06229.

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