Livia Lenzini

Livia Lenzini
University of Padua | UNIPD · Department of Medicine DIMED

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70
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Publications

Publications (70)
Article
Untreated patients affected by hereditary fructose intolerance (HFI) present an abnormal transferrin (Tf) glycosylation pattern suggestive of N-hypoglycosylation. Analysis of defects in N-glycosylation is possible by analysis of serum sialotransferrin (sialoTf) pattern. The sialoTf profile is a valuable tool to facilitate the diagnosis of HFI. Its...
Article
Disclosure: G. Pintus: None. T.M. Seccia: None. G. Rossitto: None. B. Caroccia: None. G. Ceolotto: None. L. Lenzini: None. G. Rossi: None. Background. Current guidelines suggest withdrawal of mineralocorticoid receptor antagonists (MRA) before subtyping primary aldosteronism (PA) by adrenal venous sampling (AVS), but this practice can cause severe...
Article
Full-text available
Managing Inherited Metabolic Disorders (IMDs) at risk for hypoglycemia, such as Glycogen Storage Diseases (GSDs), Hereditary Fructose Metabolism Disorders (HFMDs) and Congenital Hyperinsulinism (CH), poses challenges in dietary treatments and blood glucose monitoring. The effectiveness of Continuous Glucose Monitoring (CGM) remains a subject of ong...
Article
Background: Cytosolic and mitochondrial Ca ²⁺ concentrations are key signals for triggering the secretion of aldosterone in primary aldosteronism (PA), the most common form of secondary hypertension. Aim: To investigate [Ca ²⁺ ] i transients and oscillations in human CD56 ⁺ cells isolated from aldosterone producing adenoma (APA) and normal surround...
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Full-text available
Background: Methylmalonic Aciduria (MA) without homocystinuria (or isolated MA) is a group of rare inherited metabolic disorders which leads to the accumulation of methylmalonic acid (MMA), a toxic molecule that accumulates in blood, urine, and cerebrospinal fluid, causing acute and chronic complications including metabolic crises, acute kidney inj...
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Full-text available
The fluctuations of the intracellular Ca2+ concentration ([Ca2+]i) are key physiological signals for cell function under normal conditions and can undergo profound alterations in disease states, as high blood pressure due to endocrine disorders like primary aldosteronism (PA). However, when assessing such fluctuations several parameters in the Ca2+...
Article
Objective Primary aldosteronism (PA), a common form of secondary hypertension, is characterized by an increase of cytosolic intracellular Ca2+ concentrations [Ca2+]i. Our aim is to investigate transients and oscillations of [Ca2+]i in a human model of isolated CD56+ aldosterone-producing adenoma (APA) cells and normal surrounding adrenocortical (NA...
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Full-text available
Introduction Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing’s syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear...
Article
Drug-resistant arterial hypertension (RH) is a major risk factor for cardiovascular disease, often due to overlooked underlying causes. Identification of such causes poses significant clinical challenges. In this setting, primary aldosteronism (PA) is a frequent cause of RH and its prevalence in RH patients is likely higher than 20%. The pathophysi...
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Full-text available
Background Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraga...
Article
Objectif L’hypertension artérielle est un facteur de risque majeur de morbidité et mortalité cardiovasculaire. Contrastant avec l’hypertension essentielle, majoritaire, l’hypertension peut être secondaire au syndrome de Cushing (CS), à l’hyperaldosteronisme primaire (PA), au pheochromocytome/paragangliome (PPGL). Leur détection efficace reste fonda...
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Full-text available
Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to20% depending on the pop...
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Full-text available
Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing’s syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects a...
Article
Context Sampling of blood in the supine position for diagnosis of pheochromocytoma and paraganglioma (PPGL) results in lower rates of false-positives for plasma normetanephrine than seated sampling. It is unclear how in-patient versus out-patient testing and other preanalytical factors impact false-positives. Objective Identify preanalytical preca...
Article
An altered secretion of adrenocortical and adrenomedullary hormones plays a role in the clinical syndromes of primary aldosteronism (PA), Cushing’s and pheochromocytoma. Moreover, an altered production of adrenocortical hormones and/or an abnormal release of factors by the adrenal medulla are involved in several other diseases, including high blood...
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Full-text available
The adrenal cortex plays a key role in the regulation of metabolism, salt and water homeostasis and sex differentiation by synthesizing glucocorticoid, mineralocorticoid and androgen hormones. Evidence exists that angiotensin II regulates adrenocortical function and it has been contended that angiotensin peptides of the non-canonical branch of the...
Article
Objective Drug-resistant arterial hypertension can derive from unrecognized forms of secondary hypertension of which primary aldosteronism (PA) is one of the most common. While available data suggest a high prevalence of PA in patients with resistant hypertension (RH), its rate in such population is unclear. This study sought to establish the rate...
Article
Objective A blood pressure (BP)-independent catabolic shift upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. This study sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures in patients...
Article
Objective The angiotensin converting enzyme 2 (ACE2) and its product angiotensin-(1–7) (Ang-(1–7)) were suggested to play cardiovascular protective effects via angiotensin type 2 (AT2R), MasR and alamandine receptors. Whether this involves blunting of aldosterone biosynthesis in humans remains unknown. Design and method We quantified ACE2 mRNA in...
Article
Aims We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients s...
Article
Objective: The branch of the renin--angiotensin system constituting angiotensin-(1-7) [Ang-(1-7)], the Ang II type 2 receptor, the Mas receptors and the Ang-(1-7)-forming enzyme ACE-2, by counteracting the Ang II type 1 receptor (AT1R)-mediated effects, are held to be cardiovascular protective in several conditions. However, whether Ang-(1-7) and...
Article
Purpose Familial hyperaldosteronism type 1 (FH-1) is an autosomal dominant form of primary aldosteronism (PA), featuring a marked phenotypic heterogeneity, ranging from mild forms of PA and arterial hypertension (HT) to severe forms complicated by stroke at a young age. Affected patients usually reach the fertile age; hence, transmission of the dis...
Article
Aldosterone, the main mineralocorticoid hormone, plays a fundamental role in maintaining blood pressure (BP)and volume under hypovolemic conditions. However, in numerous diseases, where it is produced in excess, it plays a detrimental role and contributes to cardiovascular events and ultimately to death in a multitude of patients. The seminal obser...
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Full-text available
Context Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and en...
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Full-text available
Aims A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as s...
Article
Available evidence demonstrates a crosstalk between the renin–angiotensin and the parathyroid hormone–vitamin D systems. A new study suggests that vitamin D supplementation can lower systolic blood pressure and plasma aldosterone levels in patients with primary aldosteronism.
Article
Primary aldosteronism (PA) is a highly prevalent cause of arterial hypertension featuring excess cardiovascular events. A timely diagnosis and treatment of PA cures hyperaldosteronism and can provide resolution or improvement of arterial hypertension, even when the latter is resistant to drug treatment. Accordingly, strategies to screen early and w...
Article
Context: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. Objectives: To investigate in a real life study the rate of bilateral success, identification of unilateral aldosteronism and bl...
Article
Background: A metabolic shift in energy expenditure toward a catabolic state upon high sodium (Na ⁺ ) diet, ultimately favouring endogenous water accrual and body fluid preservation, has recently been described in a rodent model. Objective: To investigate the impact of high Na ⁺ intake on renal Na ⁺ /water handling and metabolic signatures in a lar...
Article
Context The G protein-coupled estrogen receptor (GPER) mediates an aldosterone secretagogue effect of 17β-estradiol in human HAC15 adrenocortical cells after estrogen receptor β blockade. As GPER mediates mineralocorticoid receptor-independent aldosterone effects in other cell types, we hypothesized that aldosterone could modulate its own synthesis...
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Full-text available
Context Accumulating evidences suggest a link between adrenocortical zona glomerulosa and parathyroid gland through mechanisms that remain unexplored. Objectives To test the hypothesis that in vivo Angiotensin (Ang) II blockade affects parathyroid hormone (PTH) secretion in hypertensive patients and that aldosterone and Ang II directly stimulate P...
Article
The angiotensin II type 2 receptor (AT2R) and the angiotensin-(1-7) receptor (MasR) play a cardiovascular protective role by counter-regulating angiotensin II type 1 receptor (AT1R)-mediated effects, but whether this involves blunting of adrenocortical hormone secretion is unknown. We investigated the presence of AT1R, AT2R and MasR in aldosterone-...
Chapter
In 2011, using exomes sequencing Choi et al. in about 34% of 22 aldosterone-producing adenoma (APA) discovered mutations in the selectivity filter of the KCNJ5 gene, which codes for the Kir3.4 K+ channel. This channel is highly expressed in the aldosterone-producing cells of the zona glomerulosa (ZG) and plays a key role in maintaining cell hyperpo...
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Full-text available
As a blunted expression of the twik-related acid-sensitive K⁺ channel 2 (TASK-2) is a common feature of aldosterone producing adenoma (APA) causing primary aldosteronism (PA), we sequenced the promoter region of the TASK-2 gene (KCNK5) in APAs (n=76), primary hypertensive patients (n=98) and 20 years-old healthy volunteers (n=71), searching for var...
Article
Background: Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization inde...
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Full-text available
Studies involving adoptive families and twins have demonstrated the genetic basis of hypertension and shown that genetic factors account for about 40% of the variance in blood pressure among individuals. Arterial hypertension is genetically complex: multiple genes influence the blood pressure phenotype through allelic effects from single genes and...
Article
Background: We meta-analysed the available studies reporting on KCNJ5 mutations in Aldosterone Producing Adenoma (APA) to determine the clinical characteristics of APA patients with a mutation of the KCNJ5 gene. Methods: We applied the PICO strategy using predefined terms (Population: primary aldosteronism patients with aldosterone producing adenom...
Article
Due to selection biases and inadequate statistical power individual studies may fail to identify the clinical features of patients with an Aldosterone Producing Adenoma (APA) harboring KCNJ5 mutations. When this failure occurs meta-analysis can provide significant outcome data. To determine the clinical features of these APA patients. We systematic...
Article
Prorenin can be detected in plasma of hypertensive patients. If detected in patients with primary aldosteronism could implicate prorenin in the development of primary aldosteronism. To address this issue, we measured the plasma prorenin levels in primary aldosteronism patients, the expression of the prorenin receptor (PRR) in the normal human adren...
Article
Primary aldosteronism (PA) is the most common endocrine cause of high blood pressure. Only a minority of the PA cases are familial and due to known (CYP11B2/CYP11B1 chimeric gene or mutations in the KCNJ5 gene) or unknown causes. In the most common sporadic cases the mechanisms by which the excess aldosterone production persists in spite of high bl...
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Full-text available
Context: Understanding the function of the KCNJ5 potassium channel through characterization of naturally occurring novel mutations is key for dissecting the mechanism(s) of autonomous aldosterone secretion in primary aldosteronism. Objective: We sought for such novel KCNJ5 channel mutations in a large database of patients with aldosterone-producing...
Article
Context: Understanding the function of the Kir3.4 (KCNJ5 gene) potassium channel through characterization of occurring novel mutations is key for dissecting the mechanism(s) of autonomous aldosterone secretion in primary aldosteronism. Objective: To identify novel KCNJ5 channel mutations and functionally characterize them in a large database of pat...
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Full-text available
Fertile women have lower blood pressure (BP) and cardiovascular risk than age-matched men, which suggests that estrogens exert cardiovascular protective effects. However, whether 17 β-estradiol blunts aldosterone secretion, and thereby affects the gender dimorphism of BP, is unknown. We therefore sought for the estrogen receptor subtypes in human a...
Article
We tested the hypothesis that variations in the PLA2G7 gene encoding the lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme deemed to have proatherogenic activity, affect the Lp-PLA2 levels and predicts cardiovascular events. Using a prospective cohort study design, we investigated incident cardiovascular events as a function of the PLA2G...
Chapter
Primary aldosteronism (PA) is the most common endocrine form of high blood pressure (BP) and causes excessive organ damage to the heart, vessels, and kidneys, which translates into an excess of cardiovascular events. When the diagnosis is made early on and an appropriate therapy is timely instituted, the hyperaldosteronism and the hypokalemia can...
Article
Full-text available
Context: The molecular mechanisms of primary aldosteronism, a common cause of human hypertension, are unknown, but alterations of K(+) channels can play a key role. Objective: The objective of the study was to investigate the following: 1) the expression of the Twik-related acid-sensitive K(+) channels (TASK) in aldosterone producing adenomas (A...
Article
Background. Fertile women have lower blood pressure and are held to be at lower risk for cardiovascular events than age-matched man. However, whether this gender dimorphism involves a modulation of aldosterone synthesis by 17 beta-estradiol (E2) is unknown. Aims. i) To investigate estrogen receptor subtypes gene expression in the normal human adren...
Article
Background and aim. The gender dimorphism in the pressor effect of hyperaldosteronism suggests that estrogens may modulate aldosterone synthesis. Estrogens were suggested to affect adrenocortical cell proliferation via beta estrogen receptor (ERβ), but it remains unknown if they also influence aldosterone synthesis. Methods. We therefore investigat...
Article
Primary aldosteronism (PA) is a common cause of secondary hypertension, because it involves 11.2% of referred hypertensive patients.1 Primary hyperparathyroidism (PPTH) is much less common, with a prevalence that, albeit imprecisely known, is probably <0.01% in unselected hypertensives. However, arterial hypertension develops in the majority (56% t...
Article
Substantial evidence supports a genetic susceptibility to develop nephropathy in type 1 diabetes and a key pathogenic role of actin cytoskeleton dysfunction in this complication. We previously reported that many cytoskeletal proteins were either up- or down-regulated in fibroblast cells from type 1 diabetic (T1DM) patients with nephropathy. The gen...
Article
The involvement of urotensin II, a vasoactive peptide acting via the G protein-coupled urotensin II receptor, in arterial hypertension remains contentious. We investigated the expression of urotensin II and urotensin II receptor in adrenocortical and adrenomedullary tumors and the functional effects of urotensin II receptor activation. The expressi...
Article
We investigated heritability of plasma levels (mass) and activity of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). In 54 healthy twins pairs we estimated genetic variance and heritability of Lp-PLA(2) mass and activity using maximum likelihood and least squares methods. We estimated intra-class correlation (ICC) and proportion of additive...
Article
Since type 1 diabetes mellitus (T1DM) patients with nephropathy (DN+) are insulin-resistant, we aimed to identify (new) potential molecular sites involved in the alterations of glucose metabolism in these patients. We examined the expression of glycolytic enzymes in cultured fibroblasts from T1DM(DN+) patients as compared to those from T1DM patient...
Article
Aldosterone-producing adenomas (APAs) are a common cause of arterial hypertension, but the underlying molecular mechanisms are unknown, although a transcriptional modulation of aldosterone synthase (CYP11B2) has been suggested. Aldosterone synthesis involves 2 main rate-limiting steps: cholesterol transport into mitochondria and CYP11B2 gene transc...
Article
Insulin can generate oxygen free radicals. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, exert a powerful antioxidant effect. The present study aimed to clarify the mechanisms through which insulin generates free radicals and to assess whether pravastatin modulates such effects. In cultured skin fibroblasts from human volunte...
Article
Context: RGS2 (regulators of G-protein signaling) is a negative regulator of Gαq protein signaling, which mediates the action of several vasoconstrictors. RGS2-deficient mouse line exhibits a hypertensive phenotype and a prolonged response to vasoconstrictors. Objective: To compare RGS2 expression in peripheral blood mononuclear cells (PBMs) and cu...
Article
Fibroblasts are involved in the remodeling of the heart and of the vasculature associated to arterial hypertension, and an abnormal extracellular signal-regulated kinase 1/2 (ERK1/2) activation by angiotensin II (Ang II) plays a pivotal role in this process. However, the intracellular pathways leading to cell hypertrophy and hyperplasia, as well as...
Article
Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure. A...
Article
Am J Hypertens (2004) 17, 07A–07A; doi: 10.1016/j.amjhyper.2004.03.010 OR-11: RGS2 expression and intracellular ca2+ mobilization in fibroblasts from hypertensive patients Michelangelo Sartori1, Giulio Ceolotto1, Livia Lenzini1, Italia Papparella1, Lorenzo A. Calò1, Elisa Pagnin1 and Andrea Semplicini11Clinical and Experimental Medicine, Padua Uni...
Article
RGSs (regulators of G-protein signaling), a family of GTPase-activating protein, increase the deactivation rate of heterotrimeric G proteins. RGS2 is a negative regulator of Gaq, which mediates the action of several physiological agonists, such as angiotensin II. Knock out mice for RGS2 gene exhibit a hypertensive phenotype and a prolonged response...
Article
Full-text available
Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variations in blood pressure. A...
Article
Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the het- erotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure....

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