New roles of aldosterone and mineralocorticoid receptors in cardiovascular disease: translational and sex-specific effects

Davel, Ana Paula; Jaffe, Iris Z.; Tostes, Rita C.; Jaisser, Frédéric; Chantemèle, Eric J. Belin de

doi:10.1152/ajpheart.00073.2018

Cited by 27 publications

(16 citation statements)

References 106 publications

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“…The aldosterone-mineralocorticoid receptor axis is present in many tissues and participates in the regulation of vascular responsiveness and immune function [29]. The mineralocorticoid (MR) and glucocorticoid receptors (GR) control metabolic, hemodynamic and stress responses throughout the body [30,31].…”

Section: Discussionmentioning

confidence: 99%

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Colleen¹

2021

J Dermatol Res Ther

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common in Caucasian women, appears near the menopausal transition or beyond, and affects the eyebrows and frontal hairline [7-10]. Targeted destruction of the pilosebaceous unit in women during reproductive aging may share proinflammatory mechanisms with hypertension. Methods This study received approval from the University of Missouri Kansas City Institutional Review Board and informed written consent was obtained from all patients. Age, BMI, race, type of hair loss, systolic and diastolic blood pressure readings and presence of antihypertensive medication were collected from each patient. Blood pressure readings were taken at every visit, in the seated position, in one arm via an automated cuff. All but one patient was seen multiple times. The highest blood pressure reading across multiple visits was recorded. Data from 43 women with scarring hair loss was collected. 22 African American women with CCCA and 21 Caucasian women with FFA were compared to an age, race and BMI matched group of women without hair loss. The control group originated from the same clinic. To support randomness in the control group, data was collected from women attending clinic on the 1 st , 15 th and 30 th days of the month. Descriptive statistics, such as mean, standard deviation and proportion were calculated to describe our sample. T tests were conducted to estimate and test group difference on the outcome variables. Statistical analyses were conducted using SPSS version 24. Results Both study groups had a mean systolic pressure of

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Section: Discussionmentioning

confidence: 99%

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Colleen¹

2021

J Dermatol Res Ther

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“…Studies in rodents have provided evidence of sex differences in the role of adipocyte-derived factors in aldosterone secretion. In obese female rats, leptin may contribute to increased BP and endothelial dysfunction by stimulating secretion of aldosterone 70,71 . However, the importance of leptininduced increases in aldosterone secretion in the setting of obesity in male rodents or in humans of either sex is still unclear.…”

Section: Aldosterone and Mr Activationmentioning

confidence: 99%

Obesity, kidney dysfunction and hypertension: mechanistic links

et al. 2019

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Excessive adiposity raises blood pressure and accounts for 65-75% of primary hypertension, which is a major driver of cardiovascular and kidney diseases. In obesity, abnormal kidney function and associated increases in tubular sodium reabsorption initiate hypertension, which is often mild before the development of target organ injury. Factors that contribute to increased sodium reabsorption in obesity include kidney compression by visceral, perirenal and renal sinus fat; increased renal sympathetic nerve activity (RSNA); increased levels of anti-natriuretic hormones, such as angiotensin II and aldosterone; and adipokines, particularly leptin. The renal and neurohormonal pathways of obesity and hypertension are intertwined. For example, leptin increases RSNA by stimulating the central nervous system proopiomelanocortin-melanocortin 4 receptor pathway, and kidney compression and RSNA contribute to renin-angiotensin-aldosterone system activation. Glucocorticoids and/or oxidative stress may also contribute to mineralocorticoid receptor activation in obesity. Prolonged obesity and progressive renal injury often lead to the development of treatment-resistant hypertension. Patient management therefore often requires multiple antihypertensive drugs and concurrent treatment of dyslipidaemia, insulin resistance, diabetes and inflammation. If more effective strategies for the prevention and control of obesity are not developed, cardiorenal, metabolic and other obesity-associated diseases could overwhelm health-care systems in the future. Obesity and its adverse consequences are major burdens to health-care systems worldwide 1. The Global Burden of Disease study, which includes data from 195 countries, reports that

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“…Cardiac myocytes appear to express very little 11-βHSD2, which means that the cardiomyocyte-residing MR may primarily be stimulated by cortisol rather than aldosterone [8]. Nevertheless, direct effects of aldosterone in cardiac myocytes have been documented and the MR plays important roles in cardiac physiology [9,10]. Since its effects are genomic, MR gene expression effects take at least several hours to manifest, but aldosterone is known to exert also more rapid, transient, non-genomic effects via other receptors, including GPER (G protein-coupled estrogen receptor) [11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease

Parker

Wertz

Pollard

et al. 2018

IJMS

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The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR’s actions, but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter’s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

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New roles of aldosterone and mineralocorticoid receptors in cardiovascular disease: translational and sex-specific effects

Cited by 27 publications

References 106 publications

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Obesity, kidney dysfunction and hypertension: mechanistic links

Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease

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