TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

Rios, F. J. et al. (2022) TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt. Communications Biology, 5, 746. (doi: 10.1038/s42003-022-03715-z) (PMID:35882956) (PMCID:PMC9325869)

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Abstract

Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg2+-permeable channel/α-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7+/Δkinase) mice. Plasma/tissue [Mg2+] and TRPM7 phosphorylation were reduced in vehicle-treated TRPM7+/Δkinase mice, effects recapitulated in aldosterone-salt-treated wild-type mice. Aldosterone-salt treatment exaggerated vascular dysfunction and amplified cardiovascular and renal fibrosis, with associated increased blood pressure in TRPM7+/Δkinase mice. Tissue expression of Mg2+-regulated phosphatases (PPM1A, PTEN) was downregulated and phosphorylation of Smad3, ERK1/2, and Stat1 was upregulated in aldosterone-salt TRPM7-deficient mice. Aldosterone-induced phosphorylation of pro-fibrotic signaling was increased in TRPM7+/Δkinase fibroblasts, effects ameliorated by Mg2+ supplementation. TRPM7 deficiency amplifies aldosterone-salt-induced cardiovascular remodeling and damage. We identify TRPM7 downregulation and associated hypomagnesemia as putative molecular mechanisms underlying deleterious cardiovascular and renal effects of hyperaldosteronism.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harvey, Dr Katie and Lopes, Dr Rheure and Zahraa, Maram and Touyz, Professor Rhian and Rios, Dr Francisco and De Lucca Camargo, Ms Livia and Harvey, Dr Adam and Montezano, Dr Augusto and Neves, Dr Karla and Zou, ZhiGuo
Authors: Rios, F. J., Zou, Z.-G., Harvey, A. P., Harvey, K. Y., Camargo, L. L., Neves, K. B., Nichol, S. E.F., Alves-Lopes, R., Cheah, A., Zahraa, M., Ryazanov, A. G., Ryazanova, L., Gudermann, T., Chubanov, V., Montezano, A. C., and Touyz, R. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Communications Biology
Publisher:Nature Research
ISSN:2399-3642
ISSN (Online):2399-3642
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Communications Biology 5: 746
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
300689Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762CAMS - Cardiovascular Science
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science