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Identifying new cellular mechanisms of mineralocorticoid receptor activation in the heart

Journal of Human Hypertension volume 35, pages 124–130 (2021)Cite this article

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Abstract

Recent studies have expanded our understanding of the actions of the mineralocorticoid receptor (MR) to a diverse array of tissue types that differ substantially from the epithelial cells of the renal nephron. In these cell types the role of the MR has been largely, but not exclusively, defined in terms of pathogenic signalling pathways leading to tissue injury and remodelling. Macrophages and cardiomyocytes are two cell types in which the MR plays a central role in the cardiac tissue response to injury, renovascular hypertension and oxidative stress for example. Macrophages are critical for resolution of tissue injury and wound healing and their pleiotropic actions are central to the development of many forms of heart, renal and vascular disease. The MR in cardiomyocytes is not only essential for the chronotropic and ionotropic actions of mineralocorticoids in the short and longer term, but also for induction of hypertrophic and proinflammatory signalling programs. The present review discusses recent studies, presented at the Aldosterone and Hypertension Satellite of the 15th Asian-Pacific Congress of Hypertension, investigating new mechanisms for MR signalling in these cells and how their dysfunction contributes to the onset and progression of cardiovascular disease and heart failure.

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Fig. 1: MR directed pathogenic pathways in DOC/salt cardiacinflammation and fibrosis—summary of cell selective MR knockouts.

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Acknowledgements

MK is supported by a Monash Graduate Scholarship, JY is supported by a Vanguard Grant (NHF) and NHMRC MRFF Early Career Fellowship. MK is supported by a Monash Post Graduate Scholarship. JY is supported by funding from the NHF and Monash Partners, PJF is supported by NHMRC GNT1143840 and MJY is supported by Diabetes Australia and the Eleanor Baker and Elise Shaw Gender Equity Fellowship, Baker Heart Heart and Diabetes Institute.

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  1. Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research and the Department of Molecular Translational Science, Monash University, Clayton, VIC, Australia

    Morag J. Young, Monica Kanki, Peter J. Fuller & Jun Yang

  2. Baker Heart and Diabetes Institute, Melborne, VIC, Australia

    Morag J. Young & Monica Kanki

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Correspondence to Morag J. Young.

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MJY, PJF and JY have received funding from Astra Zeneca but those specific studies are not part of the current review.

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This work was presented in part at the Aldosterone and Hypertension Satellite of the 15th Asian-Pacific Congress of Hypertension held in Brisbane, Australia from 24 to 27 November 2019.

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Young, M.J., Kanki, M., Fuller, P.J. et al. Identifying new cellular mechanisms of mineralocorticoid receptor activation in the heart. J Hum Hypertens 35, 124–130 (2021). https://doi.org/10.1038/s41371-020-0386-5

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