ERK1/2 MAPKs and Wnt Signaling Pathways are Independently Involved in Adipocytokine-Mediated Aldosterone Secretion

Vleugels, K.; Schinner, Sven; Krause, Darren; Morawietz, Henning; Bornstein, Stefan R.; Ehrhart‐Bornstein, Monika; Krug, AW

doi:10.1055/s-0031-1284367

Cited by 13 publications

(6 citation statements)

References 14 publications

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“…50-52 A growing body of evidence suggests that adipocytes produce and release factors, that may stimulate aldosterone release independent of renin-angiotensin. 53, 54, 55-58,59 Ehrhart-Bornstein et al have provided evidence of adipocyte secretory products that directly stimulate adrenocortical aldosterone secretion. In their studies, placing human adrenocortical cells into medium exposed to isolated adipocytes resulted in a 7-fold increase in aldosterone secretion.…”

Section: Discussionmentioning

confidence: 99%

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Dudenbostel¹,

Ghazi²,

Liu³

et al. 2016

Hypertension

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Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension (RHTN). A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with RHTN has not been previously investigated. Our objective was to determine if BMI is positively correlated with plasma aldosterone concentration (PAC), plasma renin activity (PRA), aldosterone-renin ratio (ARR), and 24-hour urinary aldosterone (24-hr UAldo) African-American (AA) and Caucasian patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with RHTN. The relation between PAC, PRA, ARR, 24-hr UAldo and BMI was investigated for the entire cohort, by gender, and race (65.3% Caucasian, 40.3% men). We demonstrate that PAC and ARR were significantly correlated to BMI (p<0.0001) across the first three quartiles, but not from the 3rd to 4th quartile of BMI. PRA was not correlated with BMI. 24-hr UAldo was positively correlated across all quartiles of BMI for the cohort (p<0.0001) and when analyzed by gender (men p<0.0001; women p=0.0013) and race (p<0.05), and stronger for men compared to women (r=0.19, p<0.001 versus r=0.05, p=0.431, p=0.028) regardless of race. In both AA and Caucasian patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in AA and Caucasian men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with RHTN.

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Section: Discussionmentioning

confidence: 99%

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Dudenbostel¹,

Ghazi²,

Liu³

et al. 2016

Hypertension

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“…HFpEF is highly prevalent in obese individuals 3, 4 and hypertension remains the major cause of HFpEF 2, 5 . Emerging evidence also indicates that factors secreted by adipocytes play a role in hypertension-related diseases 6–8 .…”

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confidence: 99%

Effects of Adiponectin on Calcium-Handling Proteins in Heart Failure With Preserved Ejection Fraction

Tanaka

Wilson

Essick

et al. 2014

Circ: Heart Failure

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Background Despite the increasing prevalence of heart failure (HF) with preserved ejection fraction (HFpEF) in humans, there remains no therapeutic options for HFpEF. Adiponectin (APN), an adipocyte-derived cytokine exerts cardioprotective actions and its deficiency is implicated in the development of hypertension and HF with reduced ejection fraction. Similarly APN deficiency in HFpEF exacerbates left ventricular hypertrophy (LVH), diastolic dysfunction and HF. However, the therapeutic effects of APN in HFpEF remain unknown. We sought to test the hypothesis that chronic APN overexpression protects against the progression of HF in a murine model of HFpEF. Methods and Results APN transgenic (APNTG) and wild-type (WT) mice underwent uninephrectomy, a continuous saline or d-aldosterone infusion and given 1.0% sodium chloride drinking water for 4-weeks. Aldosterone-infused WT mice developed HFpEF with hypertension, LVH and diastolic dysfunction. Aldosterone infusion increased myocardial oxidative stress and decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) protein expression in HFpEF. Although total phospholamban (PLN) protein expression was unchanged, there was decreased expression of PKA-dependent PLN phosphorylation at Ser16 and CaMKII-dependent PLN phosphorylation at Thr17. APN overexpression in aldosterone-infused mice ameliorated LVH, diastolic dysfunction, lung congestion and myocardial oxidative stress without affecting blood pressure (BP) and LVEF. This improvement in diastolic function parameters in aldosterone-infused APNTG mice was accompanied by preserved protein expression of PKA-dependent phosphorylation of PLN at Ser16. APN replacement prevented the progression of aldosterone-induced HFpEF, independent of BP, by improving diastolic dysfunction and modulating cardiac hypertrophy. Conclusions These findings suggest that APN may have therapeutic effects in patients with HFpEF.

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“…Adipocytes have been shown to stimulate aldosterone production by releasing soluble bioactive factors that have not yet been characterized (13,40,41). In fact, the control of mineralocorticoid secretion by fat tissue may involve two potential mechanisms.…”

Section: Methodsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

Lefebvre

Prévost

Louiset

2013

European Journal of Endocrinology

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A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.European Journal of Endocrinology 169 R115-R138

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ERK1/2 MAPKs and Wnt Signaling Pathways are Independently Involved in Adipocytokine-Mediated Aldosterone Secretion

Cited by 13 publications

References 14 publications

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Effects of Adiponectin on Calcium-Handling Proteins in Heart Failure With Preserved Ejection Fraction

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

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