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Updated: Sep 27, 2025

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Aldosterone and cardiovascular diseases
Wasita W Parksook1,2,3, Gordon H Williams1
1Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Aldosterone and its receptor (MR) are linked to heart failure, atrial fibrillation, and myocardial infarction. More research is needed to understand their roles in atherosclerosis, stroke, and thrombosis.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- Aldosterone's role in kidney function and hypertension is established.
- The involvement of aldosterone and the mineralocorticoid receptor (MR) in other cardiovascular diseases remains less understood.
- Investigating these roles is crucial for developing new therapeutic strategies.
Approach:
- Systematic review of literature from January 2011 to June 2021.
- Assessed mechanistic studies, pre-clinical data, clinical trials of MR antagonists, and genetic associations.
- Included 200 publications from an initial search of 3702 articles.
Key Points:
- Strong evidence links dysregulated aldosterone/MR to heart failure.
- Moderate associations were found between aldosterone/MR and atrial fibrillation and myocardial infarction.
- Insufficient data currently exists to confirm aldosterone/MR's role in atherosclerosis, stroke, or thrombosis.
Conclusions:
- Aldosterone/MR dysregulation plays a significant role in cardiovascular diseases beyond hypertension.
- Further research is needed to fully elucidate these relationships and explore MR modulators for treatment.
- Expanding the understanding of aldosterone/MR pathways may lead to novel therapeutic targets for cardiovascular conditions.
Abstract:
Aldosterone's role in the kidney and its pathophysiologic actions in hypertension are well known. However, its role or that of its receptor [minieralocorticoid receptor (MR)] in other cardiovascular (CV) disease are less well described. To identify their potential roles in six CV conditions (heart failure, myocardial infarction, atrial fibrillation, stroke, atherosclerosis, and thrombosis), we assessed these associations in the following four areas: (i) mechanistic studies in rodents and humans; (ii) pre-clinical studies of MR antagonists; (iii) clinical trials of MR antagonists; and (iv) genetics. The data were acquired from an online search of the National Library of Medicine using the PubMed search engine from January 2011 through June 2021. There were 3702 publications identified with 200 publications meeting our inclusion and exclusion criteria. Data strongly supported an association between heart failure and dysregulated aldosterone/MR. This association is not surprising given aldosterone/MR's prominent role in regulating sodium/volume homeostasis. Atrial fibrillation and myocardial infarction are also associated with dysregulated aldosterone/MR, but less strongly. For the most part, the data were insufficient to determine whether there was a relationship between atherosclerosis, stroke, or thrombosis and aldosterone/MR dysregulation. This review clearly documented an expanding role for aldosterone/MR's dysregulation in CV diseases beyond hypertension. How expansive it might be is limited by the currently available data. It is anticipated that with an increased focus on aldosterone/MR's potential roles in these diseases, additional clinical and pre-clinical data will clarify these relationships, thereby, opening approaches to use modulators of aldosterone/MR's action to more precisely treat these CV conditions.
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