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Review
. 2017;46(4):298-314.
doi: 10.1159/000480652. Epub 2017 Oct 10.

The Role of the Mineralocorticoid Receptor in Inflammation: Focus on Kidney and Vasculature

Zachary Belden  1 , Jeffrey A Deiuliis, Mirela Dobre, Sanjay Rajagopalan
Affiliations
Review

The Role of the Mineralocorticoid Receptor in Inflammation: Focus on Kidney and Vasculature

Zachary Belden et al. Am J Nephrol. 2017.

Abstract

Background: The remarkable success of clinical trials in mineralocorticoid receptor (MR) inhibition in heart failure has driven research on the physiological and pathological role(s) of nonepithelial MR expression. MR is widely expressed in the cardiovascular system and is a major determinant of endothelial function, smooth muscle tone, vascular remodeling, fibrosis, and blood pressure. An important new dimension is the appreciation of the role MR plays in immune cells and target organ damage in the heart, kidney and vasculature, and in the development of insulin resistance.

Summary: The mechanism for MR activation in tissue injury continues to evolve with the evidence to date suggesting that activation of MR results in a complex repertoire of effects involving both macrophages and T cells. MR is an important transcriptional regulator of macrophage phenotype and function. Another important feature of MR activation is that it can occur even with normal or low aldosterone levels in pathological conditions. Tissue-specific conditional models of MR expression in myeloid cells, endothelial cells, smooth muscle cells and cardiomyocytes have been very informative and have firmly demonstrated a critical role of MR as a key pathophysiologic variable in cardiac hypertrophy, transition to heart failure, adipose inflammation, and atherosclerosis. Finally, the central nervous system activation of MR in permeable regions of the blood-brain barrier may play a role in peripheral inflammation. Key Message: Ongoing clinical trials will help clarify the role of MR blockade in conditions, such as atherosclerosis and chronic kidney disease.

Keywords: Atherosclerosis; Cardiac hypertrophy; Central nervous system inflammation; Kidney fibrosis; Macrophage inflammation; Vascular remodeling.

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Figures

Fig. 1.
Fig. 1.
Mineralocorticoid agonism or elevated aldosterone levels have a deleterious effect on organ systems and cells relevant to cardiometabolic diseases.
Fig. 2.
Fig. 2.
Mineralocorticoid receptor agonism (ligand binding, left side) increases the classical activation of macrophages, while antagonism MRA promotes an alternative activation (right side).
Fig. 3.
Fig. 3.
Aldosterone stimulation of adipose tissue macrophages may potentiate local tissue inflammation exacerbating insulin resistance, diabetes, and atherosclerotic processes.
See this image and copyright information in PMC

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