Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte

Bienvenu, Laura A., Reichelt, Melissa E., Delbridge, Lea M. D. and Young, Morag J. (2013) Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte. Clinical Science, 125 9: 409-421. doi:10.1042/CS20130050


Author Bienvenu, Laura A.
Reichelt, Melissa E.
Delbridge, Lea M. D.
Young, Morag J.
Title Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
1470-8736
Publication date 2013-11-01
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1042/CS20130050
Open Access Status Not yet assessed
Volume 125
Issue 9
Start page 409
End page 421
Total pages 13
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Abstract MR (mineralocorticoid receptor) activation in the heart plays a central role in the development of cardiovascular disease, including heart failure. The MR is present in many cell types within the myocardium, including cardiomyocytes, macrophages and the coronary vasculature. The specific role of the MR in each of these cell types in the initiation and progression of cardiac pathophysiology is not fully understood. Cardiomyocyte MRs are increasingly recognized to play a role in regulating cardiac function, electrical conduction and fibrosis, through direct signal mediation and through paracrine MR-dependent activity. Although MR blockade in the heart is an attractive therapeutic option for the treatment of heart failure and other forms of heart disease, current antagonists are limited by side effects owing to MR inactivation in other tissues (including renal targets). This has led to increased efforts to develop therapeutics that are more selective for cardiac MRs and which may have reduced the occurrence of side effects in non-cardiac tissues. A major clinical consideration in the treatment of cardiovascular disease is of the differences between males and females in the incidence and outcomes of cardiac events. There is clinical evidence that female sensitivity to endogenous MRs is more pronounced, and experimentally that MR-targeted interventions may be more efficacious in females. Given that sex differences have been described in MR signalling in a range of experimental settings and that the MR and oestrogen receptor pathways share some common signalling intermediates, it is becoming increasingly apparent that the mechanisms of MRs need to be evaluated in a sex-selective manner. Further research targeted to identify sex differences in cardiomyocyte MR activation and signalling processes has the potential to provide the basis for the development of cardiac-specific MR therapies that may also be sex-specific.
Keyword Aldosterone
Cardiac function
Glucocorticoid
Hypertension
Inflammation
Mineralocorticoid receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Biomedical Sciences Publications
 
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