Accessible Requires Authentication Published by De Gruyter February 7, 2014

Relevance of SGK1 in structural, functional and molecular alterations produced by aldosterone in heart

Beatriz Martín-Fernández, María Valero Muñoz, Natalia de las Heras, Sandra Ballesteros and Vicente Lahera

Abstract

Aldosterone regulates sodium (Na+) and potassium (K+) transports in epithelial cells. Besides, aldosterone participates in cardiac alterations associated with hypertension, heart failure, diabetes, and other pathological alterations. One of the main cardiac alterations induced by aldosterone is cardiac hypertrophy in which different mechanisms are involved such as increased cardiomyocyte, calcium concentration, oxidative stress, and inflammatory and fibrotic mediators stimulation. Many epidemiological studies have demonstrated that left ventricular hypertrophy is associated with significantly increased risk of heart failure and malignant arrhythmias. SGK1 is a member of the serine/threonine kinase gene family that plays an important role in the absorption of Na+ and water through the Na+ channel in the apical membrane of tubular epithelial cells. SGK1 has been related to fibrotic mediator increase such as connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β) as well as inflammatory [tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β] and oxidative (NADPH oxidase) species. It has been shown that aldosterone induces SGK1 gene expression not only in kidneys but also in the heart. Supporting the central role of SGK1 in cardiac alterations induced by aldosterone, treatment with the mineralocorticoid antagonist spironolactone is able to reduce the gene expression of SGK1 in aldosterone-treated rats. Taken together, data suggest the involvement of SGK1 in a complex intracellular signaling, involving fibrotic, inflammatory, and oxidative pathways, which lead to cardiac hypertrophy and fibrosis induced by aldosterone.


Corresponding author: Beatriz Martín-Fernández, School of Medicine, Department of Physiology, Universidad Complutense, Madrid 28040, Spain, E-mail:

  1. Conflict of interest statement: None.

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Received: 2013-9-26
Accepted: 2014-1-14
Published Online: 2014-2-7
Published in Print: 2014-5-1

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