Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study

Giacchetti, Gilberta; Ronconi, Vanessa; Turchi, Federica; Angioletti, Laura; Mantero, Franco; Rilli, S; Boscaro, Marco

doi:10.1097/hjh.0b013e3280108e6f

Cited by 169 publications

(123 citation statements)

References 32 publications

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“…In particular, the ROC curve analysis showed that the best predictor of hypertension recovery after surgery is the duration of hypertension equal to or shorter than 6 years, in accordance with a recent study by Zarnegar et al (18). In this regard, we can hypothesize that aldosterone excess for long time could induce detrimental and irreversible effects on the cardiovascular system, such as cardiac fibrosis, left ventricular hypertrophy (29)(30)(31) or vascular remodeling with increased intima-media thickness (24), responsible for hypertension persistence in spite of aldosterone normalization after surgery.…”

Section: Discussionmentioning

confidence: 99%

Small tumor size as favorable prognostic factor after adrenalectomy in Conn's adenoma

Giacchetti¹,

Ronconi²,

Rilli³

et al. 2009

European Journal of Endocrinology

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Objective: Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is the most common curable form of secondary hypertension. Design: In order to evaluate blood pressure outcome after adrenalectomy for APA and to identify new favorable prognostic factors, data from 42 consecutive APA patients who underwent adrenalectomy were collected from 2005 to 2007. Methods: Renin-angiotensin-aldosterone system (upright and postsaline infusion test), serum and urinary electrolytes, office and ambulatory blood pressure monitoring were evaluated at baseline and after a follow-up of 2.7G2.2 years. Drug history and adenoma size at morphological evaluation were also collected. Results: Multiple regression analysis showed that, before surgery, patients with a small adenoma (diameter !20 mm) displayed higher postsaline aldosterone values (PZ0.0001), and lower serum potassium levels (PZ0.020), than patients with adenoma O20 mm. Before surgery, mineralocorticoid receptor (MR) antagonists were used in patients with small APA in greater percentage than patients with bigger adenomas (64 vs 30% respectively, PZ0.037). At follow-up, blood pressure normalized in 63% of the subjects. Recovered patients had a shorter duration of hypertension (PZ0.038), and a smaller adenoma size (PZ0.035). Receiver operating characteristic curves showed that a duration of hypertension %6 years and an APA size !20 mm were the best predictors of blood pressure normalization. Patients with APA !20 mm showed the complete restoration of blood pressure circadian rhythm. Conclusions: The presence of APA !20 mm, duration of hypertension equal or less than 6 years, and preoperative MR antagonists use are favorable prognostic factors for hypertension recovery after adrenalectomy.

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Section: Discussionmentioning

confidence: 99%

Small tumor size as favorable prognostic factor after adrenalectomy in Conn's adenoma

Giacchetti¹,

Ronconi²,

Rilli³

et al. 2009

European Journal of Endocrinology

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“…Patients with PA have a significantly higher prevalence of metabolic syndrome than those with essential hypertension (EHT) [10,11,12]. The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism

et al. 2015

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“…Furthermore, the prevalence of metabolic syndrome in patients with primary aldosteronism (PAL) is higher than in patients with essential hyperten sion [19,20] . Impaired insulin sensitivity was observed in patients with PAL and was ameliorated after surgery and medical treatment [21][22][23] . In addition, MR activation was linked to the renal inflammatory response in rodent models of diabetes mellitus [24] .…”

Section: Introductionmentioning

confidence: 99%

Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation

et al. 2013

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Aim: des-O-methyllasiodiplodin (DML) from Cerbera manghas has shown antagonistic activity against mineralocorticoid receptor (MR). Considering the involvement of MR in the insulin tolerance, we attempted to investigate the potential of DML in the treatment of type 2 diabetes mellitus (T2DM). Methods: Surface plasmon resonance (SPR) technology and reporter gene-based assays were used to study protein-small molecule interactions. HepG2 and 3T3-L1 cells were treated with H 2 O 2 (0.2 mmol/L) or aldosterone (10 nmol/L) for 24 h. The expression of MR in the cells was downregulated with siRNA. The anti-inflammatory effect of the compound was evaluated, respectively. db/db mice were administered DML (30 mg· kg -1 ·d -1 ) for 4 weeks. Serum biochemical parameters and insulin sensitivity were examined. The expression levels of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-6) and ROS-related genes (NADPH p47 subunit and transcriptional factor PU.1) in adipose tissues and livers were analyzed using real-time RT-PCR. Results: In HepG2 and 3T3-L1 cells, both H 2 O 2 and aldosterone markedly stimulates the expression of MCP-1, TNFα, IL-6, p47, and PU.1 genes. Co-treatment with DML (10 µmol/L) significantly reduced the H 2 O 2 -or aldosterone-induced expression of these genes. SPR-based assay confirmed the antagonistic activity of DML against the interaction between SRC-1 and MR-LBD. Furthermore, DML decreased aldosterone-induced MR transcriptional activity in a dose-dependent manner. Downregulation of MR with siRNA in the cells prevented or significantly attenuated aldosterone-stimulated expression of these genes, whereas DML did no longer affect the expression of these genes except that of IL-6. Oral administration of DML effectively reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) in db/db mice. The treatment also rectified the expression of pro-inflammatory factor and ROS-related genes in db/db mice. Conclusion: DML effectively lowers the blood glucose level in db/db mice possibly via ameliorating the expression of obesity-related pro-inflammatory cytokines, highlighting the potential of the marine natural product as a drug lead for the treatment of metabolic disorders.

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Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study

Cited by 169 publications

References 32 publications

Small tumor size as favorable prognostic factor after adrenalectomy in Conn's adenoma

Small tumor size as favorable prognostic factor after adrenalectomy in Conn's adenoma

Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism

Marine natural product des-O-methyllasiodiplodin effectively lowers the blood glucose level in db/db mice via ameliorating inflammation

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