• aldosterone
• biomarkers
• extracellular vesicles
• primary aldosteronism

• Aldosterone/metabolism
• Biomarkers/metabolism
• Extracellular Vesicles/genetics
• Extracellular Vesicles/metabolism
• Gene Expression Regulation
• Humans
• Hyperaldosteronism/diagnosis
• Hyperaldosteronism/genetics
• Hyperaldosteronism/metabolism
• Hypertension/diagnosis
• Hypertension/genetics
• Hypertension/metabolism
• MicroRNAs/genetics
• Prognosis
• Renin/metabolism

• AGP1
• Alpha-1-acid glycoprotein-1
• biomarker
• extracellular vesicles
• lipocalin
• miR-21-5p
• primary aldosteronism (PA)

The glucocorticoid receptor (GCR) and the mineralocorticoid receptor (MR) are members of the steroid receptor superfamily of hormone-dependent transcription factors. The receptors are structurally and functionally related. They are localized in the cytosol and translocate into the nucleus after ligand binding. GCRs and MRs can be co-expressed within the same cell, and it is believed that the balance in GCR and MR expression is crucial for homeostasis and plays a key role in normal adaptation. In critical illness, the hypothalamic-pituitary-adrenal axis is activated, and as a consequence, serum cortisol concentrations are high. However, a number of patients exhibit relatively low cortisol levels for the degree of illness severity. Glucocorticoid (GC) actions are facilitated by GCR, whose dysfunction leads to GC tissue resistance. The MR is unique in this family in that it binds to both aldosterone and cortisol. Endogenous GCs play a critical role in controlling inflammatory responses in critical illness. Intracellular GC concentrations can differ greatly from blood levels due to the action of the two 11β-hydroxysteroid dehydrogenase isozymes, type 1 and type 2. 11β-hydroxysteroid dehydrogenases interconvert endogenous active cortisol and intrinsically inert cortisone. The degree of expression of the two isozymes has the potential to dramatically influence local GC availability within cells and tissues. In this review, we will explore the clinical studies that aimed to elucidate the role of MR and GCR expression in the inflammatory response seen in critical illness.

• Mineralocorticoid receptor
• Glucocorticoid receptor, Critical illness
• 11beta-hydroxysteroid dehydrogenase
• Aldosterone
• Cortisol

The mineralocorticoid receptor (MR) and renin-angiotensin-aldosterone system (RAAS) are implicated in non-alcoholic liver fatty disease (NALFD). However, inflammatory mechanisms linking MR and RAAS with disease pathology remain unclear. Here we aimed to evaluate the contribution of myeloid MR to the inflammatory response in an animal model of non-alcoholic steatohepatitis (NASH), induced with a methionine-choline deficient diet (MCD).

Mice with a conditional deficiency of MR in myeloid cells (MyMRKO) and their counterpart floxed control mice (FC) were fed for 18 days with MCD or chow diet, respectively. Serum levels of aminotransferases and aldosterone levels were measured and hepatic steatosis, inflammation and fibrosis scored histologically. Hepatic triglyceride content (HTC) and hepatic mRNA levels of pro-inflammatory pro-fibrotic-associated genes were also assessed. Deep flow cytometric analysis was used to dissect the immune response during NASH development.

MyMRKO mice fed with an MCD diet exhibited reduced hepatic inflammation and lower HTC than controls. Absolute number and percentage of liver inflammatory infiltrate cells (except for CD8⁺ T lymphocytes) were similar in both MyMRKO and control mice fed with an MCD diet but expression of the costimulatory molecule CD86 by dendritic cells and the CD25 activation marker in CD8⁺ T cells were significantly reduced in MyMRKO.

Proinflammatory cells are functionally suppressed in the absence of MR. We hypothesized that loss of MR in myeloid cells reduces lipid accumulation in the liver, in part through modulating the adaptive immune response, which is pivotal for the development of steatosis.

• fatty liver
• fibrosis
• inflammation
• mineralocorticoid receptor
• myeloid cells
• non-alcoholic steatohepatitis
• steatohepatitis

• AME
• arterial hypertension
• low renin
• metabolic
• nonclassic AME

• Cortisone/metabolism
• Humans
• Hydrocortisone/metabolism
• Mineralocorticoid Excess Syndrome, Apparent/classification
• Mineralocorticoid Excess Syndrome, Apparent/metabolism
• Mineralocorticoid Excess Syndrome, Apparent/physiopathology
• Mineralocorticoids/metabolism
• Phenotype
• Prognosis

• MyD88
• TLR3
• TLR4
• TRIF
• Toll-like receptors
• angiotensin II
• cardiac hypertrophy
• hypertension
• innate immune system

• arterial hypertension
• biomarker
• exosomes
• microRNA
• sodium channels
• urine
• water-electrolyte balance

The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.