Mineralocorticoid Receptors in Vascular Disease: Connecting Molecular Pathways to Clinical Implications

McGraw, Adam P.; McCurley, Amy; Preston, Ioana R.; Jaffe, Iris Z.

doi:10.1007/s11883-013-0340-x

Cited by 23 publications

(20 citation statements)

References 94 publications

(114 reference statements)

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“…Aldosterone exerts detrimental effects in the cardiovascular system [50]. The mineralocorticoid receptor is expressed in VSMCs and mineralocorticoids stimulate vascular calcification [51,52].…”

Section: Mineralocorticoid Signaling In Vascular Tissuementioning

confidence: 99%

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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: Mineralocorticoid Signaling In Vascular Tissuementioning

confidence: 99%

“…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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“…Several other reports have also associated increased sFlt-1 and PlGF levels with renal and CV disorders, and PlGF was independently linked to increased left ventricular mass in patients with chronic kidney disease (CKD) [16]. Both sFlt-1 and PlGF were also associated with increased mortality in CKD patients [17].…”

Section: Discussionmentioning

confidence: 95%

Sflt-1 in heart failure: relation with disease severity and biomarkers

Gruson

Hermans

Ferracin

et al. 2016

Scandinavian Journal of Clinical and Laboratory Investigation

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Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p < 0.01). Concentration of sFlt-1 was related to HF severity (p < 0.001) and was correlated to NT-proBNP (ρ = 0.37, p < 0.01), soluble ST2 (ρ = 0.52, p < 0.01), Galectin-3 (ρ = 0.38, p < 0.01), aldosterone (ρ = 0.25, p = 0.01) and PTH(1-84) (ρ = 0.38, p < 0.01). Furthermore, sFlt-1 levels were associated to long-term CV risk. These results suggest a potential role of sFlt-1 in HF and its potential role as biomarker of CV risk.

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“…The effect of mineralocorticoids on blood pressure does, however, not depend on the effect of mineralocorticoids on the distal nephron [23] but is attributed in part to vascular inflammation [24,25], to enhanced endothelial stiffness, which compromises the release of nitric oxide [26,27,28,29,30] and direct effects of the mineralocorticoid receptor in vascular smooth muscle [31]. Besides leading to systemic hypertension, mineralocorticoids could foster pulmonary hypertension [32]. …”

Section: Effects Of Mineralocorticoidsmentioning

confidence: 99%

On the Pleotropic Actions of Mineralocorticoids

Läng

2014

Nephron Physiol

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Classical effects of mineralocorticoids include stimulation of Na⁺ reabsorption and K⁺ secretion in the kidney and other epithelia including colon and several glands. Moreover, mineralocorticoids enhance the excretion of Mg²⁺ and renal tubular H⁺ secretion. The renal salt retention following mineralocorticoid excess leads to extracellular volume expansion and hypertension. The increase of blood pressure following mineralocorticoid excess is, however, not only the result of volume expansion but may result from stiff endothelial cell syndrome impairing the release of vasodilating nitric oxide. Beyond that, mineralocorticoids are involved in the regulation of a wide variety of further functions, including cardiac fibrosis, platelet activation, neuronal function and survival, inflammation as well as vascular and tissue fibrosis and calcification. Those functions are briefly discussed in this short introduction to the special issue. Beyond that, further contributions of this special issue amplify on mineralocorticoid-induced sodium appetite and renal salt retention, the role of mineralocorticoids in the regulation of acid-base balance, the involvement of aldosterone and its receptors in major depression, the mineralocorticoid stimulation of inflammation and tissue fibrosis and the effect of aldosterone on osteoinductive signaling and vascular calcification. Clearly, still much is to be learned about the various ramifications of mineralocorticoid-sensitive physiology and pathophysiology.

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Mineralocorticoid Receptors in Vascular Disease: Connecting Molecular Pathways to Clinical Implications

Cited by 23 publications

References 94 publications

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Sflt-1 in heart failure: relation with disease severity and biomarkers

On the Pleotropic Actions of Mineralocorticoids

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