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Review ArticleReview Article

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

F. Jaisser and N. Farman
Rhian M. Touyz, ASSOCIATE EDITOR
Pharmacological Reviews January 2016, 68 (1) 49-75; DOI: https://doi.org/10.1124/pr.115.011106
F. Jaisser
INSERM UMR 1138 Team 1, Cordeliers Research Center, Pierre et Marie Curie University, Paris, France (F.J., N.F); and University Paris-Est Creteil, Creteil, France (F.J.)
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N. Farman
INSERM UMR 1138 Team 1, Cordeliers Research Center, Pierre et Marie Curie University, Paris, France (F.J., N.F); and University Paris-Est Creteil, Creteil, France (F.J.)
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Rhian M. Touyz
INSERM UMR 1138 Team 1, Cordeliers Research Center, Pierre et Marie Curie University, Paris, France (F.J., N.F); and University Paris-Est Creteil, Creteil, France (F.J.)
Roles: ASSOCIATE EDITOR
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Abstract

The mineralocorticoid receptor (MR) and its ligand aldosterone are the principal modulators of hormone-regulated renal sodium reabsorption. In addition to the kidney, there are several other cells and organs expressing MR, in which its activation mediates pathologic changes, indicating potential therapeutic applications of pharmacological MR antagonism. Steroidal MR antagonists have been used for decades to fight hypertension and more recently heart failure. New therapeutic indications are now arising, and nonsteroidal MR antagonists are currently under development. This review is focused on nonclassic MR targets in cardiac, vascular, renal, metabolic, ocular, and cutaneous diseases. The MR, associated with other risk factors, is involved in organ fibrosis, inflammation, oxidative stress, and aging; for example, in the kidney and heart MR mediates hormonal tissue-specific ion channel regulation. Genetic and epigenetic modifications of MR expression/activity that have been documented in hypertension may also present significant risk factors in other diseases and be susceptible to MR antagonism. Excess mineralocorticoid signaling, mediated by aldosterone or glucocorticoids binding, now appears deleterious in the progression of pathologies that may lead to end-stage organ failure and could therefore benefit from the repositioning of pharmacological MR antagonists.

Footnotes

  • This work was supported by grants from Institut National de la Santé et de la Recherche Médicale, the F-CRIN INI-CRCT: cardiovascular and Renal Clinical Trialists and the FP7-funded COST ADMIRE (BM1301) networks.

  • dx.doi.org/10.1124/pr.115.011106.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 68 (1)
Pharmacological Reviews
Vol. 68, Issue 1
1 Jan 2016
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Review ArticleReview Article

The Mineralocorticoid Receptor in Pathology

F. Jaisser and N. Farman
Pharmacological Reviews January 1, 2016, 68 (1) 49-75; DOI: https://doi.org/10.1124/pr.115.011106

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Review ArticleReview Article

The Mineralocorticoid Receptor in Pathology

F. Jaisser and N. Farman
Pharmacological Reviews January 1, 2016, 68 (1) 49-75; DOI: https://doi.org/10.1124/pr.115.011106
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  • Article
    • Abstract
    • I. Introduction
    • II. Mineralocorticoid Receptor Antagonists
    • III. Mineralocorticoid Receptor and Cardiac Diseases
    • IV. Mineralocorticoid Receptor and Vascular Diseases
    • V. Mineralocorticoid Receptor and Metabolic Diseases
    • VI. Mineralocorticoid Receptor and Renal Diseases
    • VII. Mineralocorticoid Receptor and Ocular Diseases
    • VIII. Mineralocorticoid Receptor and Skin Diseases
    • IX. Paradoxical Effects of Mineralocorticoid Receptor Activation
    • X. Common Mechanisms Involved in Pathologic Consequences Of Mineralocorticoid Receptor Activation
    • XI. Dysregulations of Mineralocorticoid Receptor Activity
    • XII. Conclusion and Open Questions
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
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