Cardiac effects of aldosterone: Does gender matter?

Mihailidou, Anastasia S.; Ashton, Anthony W.

doi:10.1016/j.steroids.2014.08.013

Cited by 24 publications

(15 citation statements)

References 97 publications

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“…The levels of aldosterone were also higher in women than in men, and were positively associated with markers of concentric remodelling, such as left ventricular wall thickness 74-76 .…”

Section: Sexual Dimorphismmentioning

confidence: 93%

Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

2015

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Insulin resistance, type 2 diabetes mellitus and associated hyperinsulinaemia can promote the development of a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Termed diabetic cardiomyopathy, this form of cardiomyopathy is a major cause of morbidity and mortality in developed nations, and the prevalence of this condition is rising in parallel with increases in the incidence of obesity and type 2 diabetes mellitus. Of note, female patients seem to be particularly susceptible to the development of this complication of metabolic disease. The diabetic cardiomyopathy observed in insulin-resistant or hyperinsulinaemic states is characterized by impaired myocardial insulin signalling, mitochondrial dysfunction, endoplasmic reticulum stress, impaired calcium homeostasis, abnormal coronary microcirculation, activation of the sympathetic nervous system, activation of the renin–angiotensin–aldosterone system and maladaptive immune responses. These pathophysiological changes result in oxidative stress, fibrosis, hypertrophy, cardiac diastolic dysfunction and eventually systolic heart failure. This Review highlights a surge in diabetic cardiomyopathy research, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies.

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“…The levels of aldosterone were also higher in women than in men, and were positively associated with markers of concentric remodelling, such as left ventricular wall thickness 74-76 .…”

Section: Sexual Dimorphismmentioning

confidence: 93%

Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

2015

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“…Indeed, in endothelial cells MR regulates the expression of the pro-inflammatory intercellular adhesion molecule-1 (ICAM-1), and this was shown to be modulated by estrogens through interaction of estrogen receptors and MR. This has been proposed as a possible mechanism protecting premenopausal women from cardiovascular disease (Barrett Mueller et al, 2014;Mihailidou and Ashton, 2014).…”

Section: Cscr: the Mineralocorticoid Pathway Hypothesismentioning

confidence: 99%

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis

Daruich

Matet

Dirani

et al. 2015

Progress in Retinal and Eye Research

819

996

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Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

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“…2, 3 There is accumulating evidence that plasma aldosterone levels are higher in overweight and hypertensive women and that the elevated plasma aldosterone is positively associated with cardiac and vascular dysfunction in females but not in males. 5-8 Mineralocorticoid excess and enhanced mineralocorticoid receptor (MR) activation promote oxidative stress, inflammation, endothelial dysfunction, arterial remodeling as well as fibrosis. 3, 9 …”

Section: Introductionmentioning

confidence: 99%

Endothelial Mineralocorticoid Receptor Mediates Diet-Induced Aortic Stiffness in Females

Jia

Habibi

Aroor

et al. 2016

Circulation Research

156

179

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Rationale Enhanced activation of the mineralocorticoid receptors (MR) in cardiovascular tissues increases oxidative stress, maladaptive immune responses and inflammation with associated functional vascular abnormalities. We previously demonstrated that consumption of a Western Diet (WD) for 16 weeks results in aortic stiffening, and that these abnormalities were prevented by systemic MR blockade in female mice. However, the cell specific role of endothelial MR (ECMR) in these maladaptive vascular effects has not been explored. Objective We hypothesized that specific deletion of the ECMR would prevent WD-induced increases in endothelial sodium channel (ENaC) activation, reductions in bioavailable nitric oxide (NO), increased vascular remodeling and associated increases in vascular stiffness in females. Methods and Results Four week-old female ECMR knockout and wild type mice were fed either mouse chow or WD for 16 weeks. WD feeding resulted in aortic stiffness and endothelial dysfunction as determined in vivo by pulse wave velocity (PWV) and ex vivo by atomic force microscopy, and wire and pressure myography. The WD-induced aortic stiffness was associated with enhanced ENaC activation, attenuated endothelial NO synthase (eNOS) activation, increased oxidative stress, a pro-inflammatory immune response and fibrosis. Conversely, cell specific ECMR deficiency prevented WD-induced aortic fibrosis and stiffness in conjunction with reductions in ENaC activation, oxidative stress and macrophage pro-inflammatory polarization, restoration of eNOS activation. Conclusions Increased ECMR signaling associated with consumption of a WD plays a key role in endothelial ENaC activation, reduced NO production, oxidative stress, and inflammation that lead to aortic remodeling and stiffness in female mice.

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Cardiac effects of aldosterone: Does gender matter?

Cited by 24 publications

References 97 publications

Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis

Endothelial Mineralocorticoid Receptor Mediates Diet-Induced Aortic Stiffness in Females

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