Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

Chen, Hui; Sun, Feng; Zhong, Xiaoshi; Shao, Yuebin; Yoshimura, Akinobu; Liu, Yan

doi:10.1159/000355736

Cited by 40 publications

(33 citation statements)

References 31 publications

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“…Recent studies documented a beneficial effect of aldosterone antagonism [50,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98]. In peritoneal dialysis patients, spironolactone treatment showed protective effects on cardiac function [99].…”

Section: Aldosterone and Vascular Calcification In Ckdmentioning

confidence: 99%

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

et al. 2014

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Vascular calcification is frequently found already in early stages of chronic kidney disease (CKD) patients and is associated with high cardiovascular risk. The process of vascular calcification is not considered a passive phenomenon but involves, at least in part, phenotypical transformation of vascular smooth muscle cells (VSMCs). Following exposure to excessive extracellular phosphate concentrations, VSMCs undergo a reprogramming into osteo-/chondroblast-like cells. Such ‘vascular osteoinduction' is characterized by expression of osteogenic transcription factors and triggered by increased phosphate concentrations. A key role in this process is assigned to cellular phosphate transporters, most notably the type III sodium-dependent phosphate transporter Pit1. Pit1 expression is stimulated by mineralocorticoid receptor activation. Therefore, aldosterone participates in the phenotypical transformation of VSMCs. In preclinical models, aldosterone antagonism reduces vascular osteoinduction. Patients with CKD suffer from hyperphosphatemia predisposing to vascular osteogenic transformation, potentially further fostered by concomitant hyperaldosteronism. Clearly, additional research is required to define the role of aldosterone in the regulation of osteogenic signaling and the consecutive vascular calcification in CKD, but more generally also other diseases associated with excessive vascular calcification and even in individuals without overt disease.

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Section: Aldosterone and Vascular Calcification In Ckdmentioning

confidence: 99%

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

et al. 2014

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“…The increase of both of these hormones in situations of acute stress is physiologically plausible, as both prepare for a ‘fight-or-flight' response. Both aldosterone [5,6] and cortisol [7] increase blood pressure. In addition, cortisol increases catabolism in order to meet the increased energy demand [8].…”

Section: Introductionmentioning

confidence: 99%

Genetic, Molecular and Clinical Determinants for the Involvement of Aldosterone and Its Receptors in Major Depression

et al. 2014

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Major depression (MDE) has metabolic and neuroendocrine correlates, which point to a biological overlap between MDE and cardiovascular diseases. Whereas the hypothalamic-pituitary-adrenocortical axis has long been recognized for its involvement in depression, the focus was mostly on cortisol/corticosterone, whereas aldosterone appears to be the ‘forgotten' stress hormone. Part of the reason for this is that the receptors for aldosterone, the mineralocorticoid receptors (MR), were thought to be occupied by glucocorticoids in most parts of the brain. However, recently it turned out that aldosterone acts selectively in relevant mood-regulating brain areas, without competing with cortisol/corticosterone. These areas include the nucleus of the solitary tract (NTS), the amygdala and the paraventricular nucleus of the hypothalamus. These regions are intimately involved in the close relationship between emotional and vegetative symptoms. Genetic analysis supports the role of aldosterone and of MR-related pathways in the pathophysiology of depression. Functional markers for these pathways in animal models as well as in humans are available and allow an indirect assessment of NTS function. They include heart rate variability, baroreceptor reflex sensitivity, blood pressure, salt taste sensitivity and slow-wave sleep. MR activation in the periphery is related to electrolyte regulation. MR overactivity is a risk factor for diabetes mellitus and a trigger of inflammatory processes. These markers can be used not only to assist the development of new treatment compounds, but also for a personalized approach to treat patients with depression and related disorders by individual dose titration with an active medication, which targets this system.

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“…Overall eplerenone has been demonstrated better profile of safety and tolerability than spironolactone [28]. The antihypertensive efficacy of both drugs are probably similar, but eplerenone shown a significant renoprotective effect in diabetic patients with hypertension [29]. Recently clinical trials have been revealed a significant reduce mortality and cardiovascular morbidity in post-myocardial infarction patients with systolic HF when eplerenone was added to the standard HF therapy [30].…”

Section: Non Selective Versus Selective Mineralocorticoid Receptor Anmentioning

confidence: 99%

The Metabolic Effects of Mineralocorticoid Receptor Antagonists in Heart Failure Patients

Berezin¹

2015

Cardiol Pharmacol

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Heart failure (HF) remains a leading cause of cardiovascular morbidity and mortality worldwide. Mineralocorticod receptor (MR) antagonists (spironolactone and eplerenone) have been studied in HF patients and in patients with acute coronary syndrome or post-myocardial infarction and left ventricular (LV) dysfunction, as well as hypertensive subjects without HF symptoms. It has suggested that mineralocorticoid receptor antagonists provide cardiovascular protection beyond its diuretic and potassium-sparing capacities. Traditionally, progression of HF relates with not full blockade of renin-angiotensin system (RAS) activation and with so called "escape" phenomenon of neurohumoral activation from effects of angiotensin converting enzyme / angiotensin receptor blockers and beta-adrenoblockers. Circulating and local aldosteron over production is discussed a main cause of none adequate effect of RAS blockade contributed negative cardiovascular remodelling and worse survival. During the last decade, several studies have shown that completed control for RAS activation might be achieved through adding MR antagonists in contemporary treatment scheme. This approach raises survival and leads to a trend in declined mortality rate in patients with HF various etiologic causes. Therefore, there are increasing evidence that both MR antagonists spironolactone and eplerenone might have a different metabolic effect in HF patients and that this difference is required to pay attention in creating of optimal HF therapeutic program. The aim of the mini review is to evaluate clinically significance of metabolic effects of mineralocorticoid receptor antagonists in HF patients.

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Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

Cited by 40 publications

References 31 publications

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Genetic, Molecular and Clinical Determinants for the Involvement of Aldosterone and Its Receptors in Major Depression

The Metabolic Effects of Mineralocorticoid Receptor Antagonists in Heart Failure Patients

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