Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

Muñoz‐Durango, Natalia; Vecchiola, Andrea; González-Gómez, Luis-Martin; Simón, Felipe; Riedel, Claudia A.; Fardella, Carlos E.; Kalergis, Alexis M.

doi:10.1155/2015/652738

Cited by 51 publications

(28 citation statements)

References 146 publications

(179 reference statements)

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“…Surprisingly, we also revealed that ApoE-KO mice treated with aldosterone display instead an increase of peripheral Tregs, presumably due to their recruitment at the plaque region to suppress the inflammation promoted by aldosterone. It is well-known, indeed, that this hormone is associated with vascular infiltration of immune cells, reactive oxidative stress, and pro-inflammatory cytokine production (59).…”

Section: Discussionmentioning

confidence: 99%

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease

et al. 2020

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Atherosclerosis is a progressive vascular disease representing the primary cause of morbidity and mortality in developed countries. Formerly, atherosclerosis was considered as a mere passive accumulation of lipids in blood vessels. However, it is now clear that atherosclerosis is a complex and multifactorial disease, in which the involvement of immune cells and inflammation play a key role. A variety of studies have shown that autophagy-a cellular catalytic mechanism able to remove injured cytoplasmic components in response to cellular stress-may be proatherogenic. So far, in this context, its role has been investigated in smooth muscle cells, macrophages, and endothelial cells, while the function of this catabolic protective process in lymphocyte functionality has been overlooked. The few studies carried out so far, however, suggested that autophagy modulation in lymphocyte subsets may be functionally related to plaque formation and development. Therefore, in this research, we aimed at better clarifying the role of lymphocyte subsets, mainly regulatory T cells (Tregs), in human atherosclerotic plaques and in animal models of atherosclerosis investigating the contribution of autophagy on immune cell homeostasis. Here, we investigate basal autophagy in a mouse model of atherosclerosis, apolipoprotein E (ApoE)-knockout (KO) mice, and we analyze the role of autophagy in driving Tregs polarization. We observed defective maturation of Tregs from ApoE-KO mice in response to tumor growth factor-β (TGFβ). TGFβ is a well-known autophagy inducer, and Tregs maturation defects in ApoE-KO mice seem to be related to autophagy impairment. In this work, we propose that autophagy underlies Tregs maturation, advocating that the study of this process in atherosclerosis may open new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease

et al. 2020

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“…MR blockade with eplerenone (an MR antagonist) has been demonstrated to rectify the reductions in the mRNA expressions of adiponectin and PPARγ that are induced by aldosterone in adipocytes. However, contrasting results have demonstrated that pretreatment with eplerenone does not affect the reduction in the adiponectin mRNA level that is induced by aldosterone [15,16].…”

Section: Introductionmentioning

confidence: 94%

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

Wang

Zhou

et al. 2016

Cell Physiol Biochem

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Background/Aims: Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms. Methods: The effects of aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator-activated receptor (PPAR) α agonist, and a p38 mitogen-activated protein kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the mRNA and protein levels in vitro and in vivo. Results: Our data revealed that aldosterone reduced the expression of adiponectin and inhibited the transport of glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo, MR blockade improved insulin-sensitive parameters and increased adiponectin expression in the myocardia of high-fat diet rats. Furthermore, aldosterone promoted p38MAPK expression but negatively affected PPARα expression, and the downregulation of adiponectin by aldosterone was reversed by MR blockade, a PPARα agonist, and a p38 MAPK inhibitor. Conclusion: The above results suggested that aldosterone promoted insulin resistance in the heart and that this effect could be partly reversed by MR blockade through signal transduction in the P38 MAPK pathway and PPARα.

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“…MR is also expressed by cells of the immune system and may modulate immune cell function. Aldosterone also has been associated with proinfl ammatory immune effects, such as the release of proinfl ammatory cytokines, generating oxidative stress and inducing fi brosis [ 88 ] . MR can regulate NF-κβ pathway(s) through activation of serum-and glucocorticoid-inducible protein kinase-1 (SGK1) [ 98 ] .…”

Section: Discussionmentioning

confidence: 99%

Differences in Gene Expression and Gene Associations in Epicardial Fat Compared to Subcutaneous Fat

Yim

Rabkin

2017

Horm Metab Res

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Epicardial adipose tissue (EAT) plays a role in cardiac physiology and may contribute to the development of coronary artery disease. Our objective was to determine whether there was a significant difference in gene expression in EAT compared to subcutaneous adipose tissue (SAT) and to identify potential relationships. MEDLINE and EMBASE were searched using the key terms "Epicardial Adipose Tissue" or "Epicardial Fat" in combination with "RNA", "mRNA", or "gene". The entry criteria were studies that presented primary data including expression levels of mRNA in human EAT compared with SAT and an expression of variance (SD). Genes identified by 2 or more studies were evaluated. Genes that showed significant change in expression between EAT and SAT were examined using the Gene Functional Classification analytical tool in Database for Annotation, Visualization and Integrated Discovery and cross-validated by ToppGene. Seventeen genes were identified from 25 studies. Meta-analysis showed that 10 genes (ADORA1, adiponectin, AGT, ADM, CATA, IL-1β, MCP-1, RBP-4, TNF-α, UCP-1) were significantly different in EAT. Gene Functional Classification analysis yielded 23 clusters with significant relationships. The top clusters were focused on responses to glucocorticoid stimulus, regulation of apoptosis, cellular ion homeostasis, and responses to hormone stimulus. Genetic analysis shows that EAT is discretely different from SAT. ADORA1, adiponectin, AGT, ADM, CATA, IL-1β, MCP-1, RBP-4, TNF-α, and UCP-1 may play significant roles in the unique physiology of EAT and/or its role in pathophysiology, through mechanisms as diverse as steroid hormone responses and regulation of apoptosis.

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Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

Cited by 51 publications

References 146 publications

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

Differences in Gene Expression and Gene Associations in Epicardial Fat Compared to Subcutaneous Fat

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