Publications by authors named "Andrea Semplicini"

84 Publications

Mild Hyperuricemia: To Treat, or Not to Treat, That is the Question. Suggestions form the URRAH Study.

High Blood Press Cardiovasc Prev 2020 Apr 23;27(2):119-120. Epub 2020 Mar 23.

Department of Medicine (DIMED), University of Padua, via S. Mattia 20, 35121, Padua, Italy.

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http://dx.doi.org/10.1007/s40292-020-00376-zDOI Listing
April 2020

Should We Increase Trust in Cardiovascular Prevention?

High Blood Press Cardiovasc Prev 2019 08 9;26(4):351-352. Epub 2019 Jul 9.

Department of Medicine (DIMED), University of Padua, Via Giustiniani 2, 35128, Padua, Italy.

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http://dx.doi.org/10.1007/s40292-019-00328-2DOI Listing
August 2019

Searching cerebrovascular risk indicators for hypertensive patients: Is Framingham Stroke Risk Profile "the magic bullet"?

J Clin Hypertens (Greenwich) 2018 02 22;20(2):246-247. Epub 2018 Jan 22.

Department of Medicine, University of Padua, Padua, Italy.

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http://dx.doi.org/10.1111/jch.13176DOI Listing
February 2018

Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair.

Congenit Heart Dis 2017 Jan 7;12(1):74-83. Epub 2016 Sep 7.

Pediatric Cardiology Unit, Department of Women's and Children's Health, University of Padua, Padova, Italy.

Background: Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%-40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal.

Methods: Eight female sheep completed the study and a stent was implanted in four. Every 3 mo we measured blood pressure of the anterior and posterior limbs and left ventricular function by echocardiography. Twelve months later invasive pressure was measured under baseline and simulated stress conditions. Expression of genes indicating oxidative stress (OS), endothelial dysfunction (ED) and stiffness, as well as pathological examination were performed in ascending (ASAO) and descending aorta (DSAO).

Results: SOD1 and MMP9 gene expression were higher in ASAO of the stented animals, compared to DSAO and controls, while NOS3 was decreased. No differences were found in blood pressure and echocardiographic parameters. No histological differences were found in the aorta of the two groups of animals.

Conclusions: Stent does not affect central and peripheral hemodynamics, cardiac structure and function even in the long term. However, the finding of markers of OS and increased stiffness of ASAO, proximal to the stent, points to molecular mechanisms for increased cardiovascular risk of patients with stented CoAo.
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http://dx.doi.org/10.1111/chd.12406DOI Listing
January 2017

Cerebral White Matter Lesions as a Clinically Relevant Intermediate Target of Cerebrovascular Prevention.

J Clin Hypertens (Greenwich) 2015 Sep 1;17(9):699-700. Epub 2015 Jun 1.

Department of Medicine, University of Padua, Padua, Italy.

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http://dx.doi.org/10.1111/jch.12584DOI Listing
September 2015

G-Protein β3-Subunit Gene C825T Polymorphism and Cardiovascular Risk: An Updated Review.

High Blood Press Cardiovasc Prev 2015 Sep 23;22(3):225-32. Epub 2015 Apr 23.

Department of Medicine, University of Padua, Padua, Italy,

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 susceptibility to hypertension, obesity and insulin resistance syndrome. A polymorphism (825C/T) in exon 10 of the GNB3 gene, encoding for the Gβ3 subunit, has been described. The 825T allele is associated with alternative splicing of the gene and formation of a truncated but functionally active β3 subunit. Many studies have investigated whether carriers of the 825T allele are at increased risk for hypertension, obesity, insulin-resistance and left ventricular hypertrophy with apparently conflicting results. The present review demonstrates that GNB3 825T allele is a useful genetic marker for better defining the risk profile of hypertensive patients, as it is associated with increased risk of stroke and myocardial infarction in longitudinal studies in Caucasians.
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http://dx.doi.org/10.1007/s40292-015-0093-4DOI Listing
September 2015

NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusion-induced apoptosis.

Vascul Pharmacol 2015 Jul 9;70:35-44. Epub 2015 Apr 9.

Department of Medicine-DIMED, University of Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy. Electronic address:

Ischemia-reperfusion (IR) leads to severe organ injury and dysfunction. Sirtuins (SIRTs) are a family of histone deacetylases (HDACs) that require nicotinamide adenine dinucleotide (NAD(+)) for the deacetylation reaction. SIRTs play a major role in counteracting cellular stress and apoptosis. This study aimed to investigate the mechanisms of heart protection against apoptosis by SIRTs and the molecular pathways involved in SIRTs regulation and function in a rat model of IR injury. Hearts of male Wistar-Kyoto rats were subjected to 30-min ischemia followed by reperfusion up to 6h. IR increased cardiomyocyte apoptosis; the cleavage of caspase 3, induced a transient upregulation of SIRT1 and downregulation of SIRT6 expression, but decreased SIRT1 activity and reduced NAD(+) content. IR also increased forkhead box protein O1 (FoxO1) expression and FoxO1 binding to SIRT1 promoter region. Resveratrol restored SIRT1 activity and NAD(+) level by an AMPK-dependent mechanism, reduced cardiomyocyte apoptosis, and attenuated caspase 3 cleavage via heat shock factor-1 deacetylation and heat shock protein (HSP) expression upregulation. Our data show new potential molecular mechanisms of up and downstream regulation of SIRT1 in IR. The interplay among FoxO1, SIRT1, NAD(+), AMPK, HSP, and SIRT6 depicts a complex molecular network that protects the heart from apoptosis during IR and may be susceptible to therapeutic interventions.
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http://dx.doi.org/10.1016/j.vph.2015.02.004DOI Listing
July 2015

An update on hypertensive emergencies and urgencies.

J Cardiovasc Med (Hagerstown) 2015 May;16(5):372-82

aDepartment of Clinical and Experimental Sciences University of Brescia, 25100 Spedali Civili, Brescia bDepartment of Medical-Surgery Sciences and Translational Medicine, Emergency Department, University La Sapienza, Sant'Andrea Hospital Rome, Rome cDepartment of Internal Medicine and Therapeutics, University of Pavia, Lombardy dDepartment of Internal Medicine 1, USL12 Veneziana, Venice eDepartment of Medicine, University of Padua, Padova fDepartment of ScienzeMediche e Chirurgiche, S.Orsola-Malpighi University Hospital, Bologna gDivision of Cardiology, Department of Medicina Clinica e Molecolare, University Roma 'Sapienza' - Azienda Ospedaliera Sant'Andrea, and IRCCS Neuromed, Rome hDivision of Cardiology, AOU Sassari, Sassari iDepartment of Cardiovascular Diseases, University of Siena, Tuscany jCardiovascular Disease Section, Department of Emergency and Organ Tranplantation, University of Bari, Bari kAS Department of Cardiology, Brindisi District, Brindisi lDepartment of Clinical and Experimental Medicine, University of Florence, Florence mDepartment of Internal Medicine and Cardiovascular Diseases, University of Palermo, Palermo nDipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università di Pisa, Pisa, Italy.

Severe acute arterial hypertension is usually defined as 'hypertensive crisis', although 'hypertensive emergencies' or 'hypertensive urgencies', as suggested by the Joint National Committee and the European Society of Hypertension, have completely different diagnostic and therapeutic approaches.The prevalence and demographics of hypertensive emergencies and urgencies have changed over the last four decades, but hypertensive emergencies and urgencies are still associated with significant morbidity and mortality.Different scientific societies have repeatedly produced up-to-date guidelines; however, the treatment of hypertensive emergencies and urgencies is still inappropriate, with potential clinical implications.This review focuses on hypertensive emergencies and urgencies management and treatment, as suggested by recent data.
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http://dx.doi.org/10.2459/JCM.0000000000000223DOI Listing
May 2015

Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study.

Pharmacogenomics 2014 Sep;15(13):1643-52

Hypertension & Related Disease Centre, AOU-University of Sassari, Sassari, Italy.

Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis.

Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach.

Materials & Methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples.

Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10(-8)). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort.

Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension.
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http://dx.doi.org/10.2217/pgs.14.119DOI Listing
September 2014

Sirtuin 1 stabilization by HuR represses TNF-α- and glucose-induced E-selectin release and endothelial cell adhesiveness in vitro: relevance to human metabolic syndrome.

Clin Sci (Lond) 2014 Oct;127(7):449-61

*Department of Medicine-DIMED, University of Padova, Padova, Italy.

Chronic inflammation and hyperglycaemia, typical features of metabolic diseases, trigger endothelial damage and release of E-selectin, a marker of endothelial activation. In the present study, we investigated molecular pathways involved in the regulation of endothelial cell activation induced by tumour necrosis factor-α (TNF-α) and high glucose. In cultured human umbilical vein endothelial cells (HUVECs), we studied the role of HuR, an ELAV (embryonic lethal, abnormal vision, Drosophila) family RNA-binding protein, and Sirtuin 1 (SIRT1) on E-selectin release and cell adhesion at different glucose concentrations. HuR expression and binding to SIRT1 were also analysed ex vivo in peripheral blood mononuclear cells (PBMCs) of subjects with and without the metabolic syndrome (MS), by immunoprecipitation (IP) of the ribonucleoprotein (RNP) complex. We found that SIRT1 overexpression prevented TNF-α- and high-glucose-dependent nuclear factor-κB (NF-κB)-p65 acetylation, E-selectin promoter activity, E-selectin release and adhesion of THP-1 cells to HUVECs. The same was mimicked by HuR overexpression, which binds and stabilizes SIRT1 mRNA. Importantly, in PBMCs of individuals with MS compared with those without, SIRT1 expression was lower, and the ability of HuR to bind SIRT1 mRNA was significantly reduced, while plasma E-selectin was increased. We conclude that post-transcriptional stabilization of SIRT1 by HuR represses inflammation- and hyperglycaemia-induced E-selectin release and endothelial cell activation. Therefore, increasing SIRT1 expression represents a strategy to counter the accelerated vascular disease in metabolic disorders.
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http://dx.doi.org/10.1042/CS20130439DOI Listing
October 2014

Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial.

Am J Emerg Med 2014 Apr 3;32(4):334-41. Epub 2014 Jan 3.

Emergency Department, Sant'Andrea Hospital, School of Medicine and Psychology "Sapienza" Univesity, Rome, Italy. Electronic address:

Introduction: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea.

Methods: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF).

Results: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days.

Conclusions: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.
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http://dx.doi.org/10.1016/j.ajem.2013.12.045DOI Listing
April 2014

Padova Hospitale Onlus: report of a 15-year experience in surgical and medical assistance in developing countries.

Ann Plast Surg 2013 Jul;71(1):6-9

Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

Nowadays, an urgent need for global medical cooperation and assistance still bears on health care providers. Because plastic, reconstructive, and aesthetic surgery is a surgical specialty with social purposes, the humanitarian importance of the discipline is, nowadays, stronger than ever. Padova Hospitale Onlus is a nonprofit charity association with the aim to ensure sustainable medical programs, in particular in the field of plastic and reconstructive surgery. The activity of the association in fund-raising strategies, volunteer enrollment, and operative strategies has been reviewed and reported to stimulate further collaboration, emulation, and contributions. Since 1996, the association has assisted over 20,000 people during 50 missions over the 5 continents, performing more than 2000 surgical operations and almost 8000 medical examination, involving more than 320 volunteers, supplying health care material or health care facilities. Furthermore, a high rate of surgical records and of medical assistance has been performed in the last 2 years, depicting a positive rising trend of activity. However, scarce financial means, absence of a structured coordination, and/or cooperation between associations may often affect the long-term sustainability of these interventions. Thus, only an experienced and structured association may grant the required resources to sustain adequate and fruitful short-term or long-term projects for the promotion of a humanitarian cooperation as much "demand driven" as possible.
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http://dx.doi.org/10.1097/SAP.0b013e318244efd2DOI Listing
July 2013

Outcome after acute ischemic stroke (AIS) in older patients: effects of age, neurological deficit severity and blood pressure (BP) variations.

Arch Gerontol Geriatr 2011 May-Jun;52(3):e185-91. Epub 2010 Dec 8.

Department of Medical and Surgical Sciences, Division of Geriatrics, Ospedale Giustinianeo (2° piano), via Giustiniani 2, I-35100 Padova, Italy.

The goal of this study was to examine the relationship between BP variations and neurological deficit outcome in old-old patients after AIS. Fifty-four patients (66-96 years), admitted consecutively for stroke were assessed, using a non-invasive BP monitoring (NIBPM), measuring mean systolic (SBP) and diastolic (DBP) blood pressure and their variation between days 1 and 7. Neurological assessment and cognitive function were evaluated using the NIH stroke Scale (NIHSS) and the short portable mental status Questionnaire (SPMSQ), respectively. Functional status was assessed using the modified Rankin scale (RS) and the Barthel index (BI). NIHSS on the 1st day positively correlated with SPMSQ score and with BI on day 21. The NIHSS variation (ΔNIHSS) between days 21 and 1 negatively correlated with mean 24-h BP change between days 7 and 1 (r=-0.59 for DBP and r=-0.54 for SBP; p<0.001). Age, severity of stroke at admission, history of hypertension, atrial fibrillation (AF) and BP levels at admission were not correlated to ΔNIHSS. An inverse correlation between the decrease of 24-h BP within the first week and ΔNIHSS suggests prudence in lowering BP in the acute phase of stroke in elderly.
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http://dx.doi.org/10.1016/j.archger.2010.11.002DOI Listing
August 2011

Interplay between miR-155, AT1R A1166C polymorphism, and AT1R expression in young untreated hypertensives.

Am J Hypertens 2011 Feb 21;24(2):241-6. Epub 2010 Oct 21.

Department of Clinical and Experimental Medicine, University of Padova Medical School, Italy.

Background: A silent polymorphism (+1166 A/C single-nucleotide polymorphism) localized in the 3'-UTR (untranslated region) of the human angiotensin II type-1 receptor (AT1R) has been associated with hypertension and cardiovascular complications. The +1166 A/C is recognized by a specific microRNA-155 (miR-155), which is base-pairing complementary with the +1166 A-allele but not with the mutant +1166 C allele. Aim of our study was to investigate the interplay between miR-155 and AT1R protein expression.

Methods: Sixty-four subjects were selected for the +1166 A/C from the cohort of hypertensives (n = 573) of the Hypertension and Ambulatory Recording Venetia Study (HARVEST): 25 were homozygous for the 1166 A allele, 20 heterozygous, and 19 homozygous for the 1166 C allele.

Results: miR-155 expression was significantly decreased in subjects with CC genotype in comparison to AA and AC genotype. AT1R protein expression was significantly increased in the CC group in comparison to AA and AC (P < 0.01) although AT1R mRNA expression was not significantly different in the three groups. AT1R protein expression was positively correlated with systolic and diastolic blood pressure and negatively correlated with miR-155 expression level. Plasma transforming growth factor-β1 (TGF-β1) may have a modulator role in the interplay between miR-155 and AT1R protein expression as it was correlated negatively with miR-155 expression and positively with AT1R protein expression in subjects with CC genotype.

Conclusion: The interplay between miR-155 expression, +1166C polymorphism, and AT1R protein expression may have a role in the regulation of blood pressure.
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http://dx.doi.org/10.1038/ajh.2010.211DOI Listing
February 2011

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study.

Crit Care 2010 16;14(3):R116. Epub 2010 Jun 16.

Emergency Medicine Department, II Medical School University La Sapienza, Sant'Andrea Hospital, via di Grottarossa, 1039 Roma 00189, Italy.

Introduction: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF).

Methods: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value < 0.05 was considered statistically significant.

Results: BNP median (interquartile range (IQR)) value at admission was 822 (412 - 1390) pg\mL; at 24 hours was 593 (270 - 1953) and at discharge was 325 (160 - 725). A BNP reduction of >46% at discharge had an area under curve (AUC) of 0.70 (P < 0.001) for predicting future adverse events. There were 78 events through follow up and in 58 of these patients the BNP level at discharge was >300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P < 0.001). The odds ratio of the patients whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P < 0.002). The odds ratio of the patients whose BNP level at discharge was >300 pg/mL and whose percentage decrease at discharge was <46% compared to the group whose BNP level at discharge was <300 pg/mL and whose percentage decrease at discharge was >46% was 9.614 (CI 4.51 - 20.47, P < 0.001).

Conclusions: A reduction of BNP >46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF.
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http://dx.doi.org/10.1186/cc9067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911763PMC
January 2011

RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients.

J Hypertens 2010 May;28(5):1104-8

Clinica Medica 4, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.

Objective: RGS2 (regulators of G-protein signalling) is a negative regulator of Galphaq protein signalling, which mediates the action of several vasoconstrictors. Low RGS2 expression increases G-protein-coupled signalling in hypertensive patients. The aim of the present study was to correlate RGS2 expression in peripheral blood mononuclear cells (PBMs) with response to antihypertensive therapy in never-treated patients with essential hypertension.

Methods And Design: RGS2 expression was measured by real-time quantitative RT-PCR in peripheral blood mononuclear cells (PBMs) from 102 essential hypertensives. The diagnosis of essential hypertension was based on all clinically required tests, including the captopril suppression test. Antihypertensive treatment was given in accordance to international guidelines. End-point of the study was systolic blood pressure (BP) less than 140 mmHg and diastolic BP less than 90 mmHg with three or less different antihypertensive agents, which identified responders to treatment. Resistant hypertension was defined as the failure to control systolic and/or diastolic BP despite at least three different classes of antihypertensive agents, including a diuretic.

Results: During follow-up, 85 (83%) patients reached the end point (responders). Resistant hypertensives (n = 17, 17%) were older, had higher baseline BP, plasma aldosterone and aldosterone: renin ratio (ARR) and lower plasma renin activity than patients who reached the end point. RGS2 was negatively correlated to systolic BP at enrollment and significantly lower in PBMs from resistant hypertensives in comparison with patients that reached BP goal. According to logistic regression analysis, high RGS2 expression was predictor of reaching BP goal, whereas high ARR after captopril, age and systolic pressure at enrolment were predictor of resistant hypertension.

Conclusion: RGS2 expression affects the response to antihypertensive treatment. Reduced RGS2 expression contributes to resistance to antihypertensive agents through poor negative feedback on the effects of aldosterone and of other vasoactive agents.
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http://dx.doi.org/10.1097/HJH.0b013e328339930fDOI Listing
May 2010

Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms.

Diabetes 2010 Apr 12;59(4):1006-15. Epub 2010 Jan 12.

Department of Clinical and Experimental Medicine, Metabolic Diseases, University of Padova, Padova, Italy.

Objective: Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that regulate metabolism and life span. We used peripheral blood mononuclear cells (PBMCs) to determine ex vivo whether insulin resistance/metabolic syndrome influences SIRTs. We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro.

Research Design And Methods: SIRT1-SIRT7 gene and protein expression was determined in PBMCs of 54 subjects (41 with normal glucose tolerance and 13 with metabolic syndrome). Insulin sensitivity was assessed by the minimal model analysis. Subclinical atherosclerosis was assessed by carotid intima-media thickness (IMT). In THP-1 cells exposed to high glucose or fatty acids in vitro, we explored SIRT1 expression, p53 acetylation, Jun NH(2)-terminal kinase (JNK) activation, NAD(+) levels, and nicotinamide phosphoribosyltransferase (NAMPT) expression. The effects of SIRT1 induction by resveratrol and of SIRT1 gene silencing were also assessed.

Results: In vivo, insulin resistance and metabolic syndrome were associated with low PBMC SIRT1 gene and protein expression. SIRT1 gene expression was negatively correlated with carotid IMT. In THP-1 cells, high glucose and palmitate reduced SIRT1 and NAMPT expression and reduced the levels of intracellular NAD(+) through oxidative stress. No effect was observed in cells exposed to linoleate or insulin. High glucose and palmitate increased p53 acetylation and JNK phosphorylation; these effects were abolished in siRNA SIRT1-treated cells. Glucose- and palmitate-mediated effects on NAMPT and SIRT1 were prevented by resveratrol in vitro.

Conclusions: Insulin resistance and subclinical atherosclerosis are associated with SIRT1 downregulation in monocytes. Glucotoxicity and lypotoxicity play a relevant role in quenching SIRT1 expression.
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http://dx.doi.org/10.2337/db09-1187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844808PMC
April 2010

Obsessive-Compulsive and Post Traumatic Avoidance Symptoms Influence the Response to Antihypertensive Therapy: Relevance in Uncontrolled Hypertension.

Pharmaceuticals (Basel) 2009 Nov 16;2(3):82-93. Epub 2009 Nov 16.

Division of General Medicine, SS. Giovanni e Paolo Hospital, Campo SS. Giovanni e Paolo, Castello 6777-30122 Venezia, Italy.

Aim: To investigate the association of uncontrolled hypertension with psychological factors associated with high cardiovascular morbidity and mortality (type D personality, depression, posttraumatic stress-related symptoms).

Methods: 205 consecutive outpatient hypertensives completed three questionnaires evaluating Type D personality (DS 16), post traumatic symptoms (revised Impact of Events Scale), symptoms of anxiety, hostility, depression and obsessive-compulsive traits (subscales of the Symptom Checklist). Uncontrolled hypertension was diagnosed when clinic sitting blood pressure was above 140/90 mmHg (130/80 in the presence of diabetes or nephropathy), despite reported adherence to treatment with at least three antihypertensive medications, including a diuretic.

Results: Uncontrolled hypertension (39%), was predicted by lower scores at Symptom Checklist obsessive-compulsive subscale and higher number of post traumatic avoidance symptoms, older age, diabetes, higher systolic pressure at first visit and longstanding hypertension. Type D personality correlated with depression, hostility, anxiety, compulsiveness, history of malignancy, and older age, but not with uncontrolled hypertension.

Conclusions: Uncontrolled hypertension is associated with low obsessionality and avoidance symptoms, which reduce compliance to treatment. On the contrary, type D personality is not correlated with uncontrolled hypertension, as it includes compulsiveness, which improves compliance. A multidisciplinary approach to the hypertensive patient is mandatory to establish if the psychological profile affects compliance.
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http://dx.doi.org/10.3390/ph2030082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978534PMC
November 2009

High-altitude cerebral effects: risks and mechanisms.

Lancet Neurol 2009 Jul;8(7):604; author reply 605

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http://dx.doi.org/10.1016/S1474-4422(09)70159-0DOI Listing
July 2009

Evidence based medicine or interpretation of evidence based medicine?

Intern Emerg Med 2009 Apr 4;4(2):97-8. Epub 2008 Dec 4.

Department of Clinical and Experimental Medicine, University of Padova, Italy.

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http://dx.doi.org/10.1007/s11739-008-0215-2DOI Listing
April 2009

Angiotensin II type 1 receptor gene polymorphism predicts development of hypertension and metabolic syndrome.

Am J Hypertens 2009 Feb 20;22(2):208-14. Epub 2008 Nov 20.

Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica 4, University of Padova, Padova, Italy.

Background: The aim of the study was to investigate the effect of polymorphism A1166C for AGTR1 and -1332G/A for AGTR2 on the incidence of sustained hypertension (HT) and metabolic syndrome in a cohort of young patients screened for stage 1 HT.

Methods: We assessed 420 white hypertensive subjects never treated for HT and followed up for 7.3 years in the HT and Ambulatory Recording Venetia Study (HARVEST). Incident physician-diagnosed HT, increase in ambulatory blood pressure (BP), and new onset metabolic syndrome were the outcome measures.

Results: For AGTR1, 37.2% of the subjects in the group with AA genotype, 47.5% in the group with AC genotype, and 66.7% in the group with CC genotype developed HT during follow-up (P = 0.001). Ambulatory systolic (P = 0.007) and diastolic (P < 0.001) BPs increased largely in the patients with CC genotype than in the rest of the group. New onset metabolic syndrome during follow-up (n = 30, P = 0.008), and the frequency of the metabolic syndrome at the end of follow-up (n = 65, P = 0.002) were also more common among the patients with CC and AC genotype. In a Cox analysis, subjects with CC genotype had an increased risk of developing HT (hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.2-2.0, P = 0.000) and metabolic syndrome (HR 2.8, 1.5-5.2, P = 0.002) than AA subjects. No association was found between the AGTR2 polymorphism and any outcome measure.

Conclusions: The AGTR1 A1166C polymorphism may be considered a genetic marker predisposing to an increase in BP and the development of the metabolic syndrome in subjects screened for stage 1 HT.
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http://dx.doi.org/10.1038/ajh.2008.319DOI Listing
February 2009

An abnormal gene expression of the beta-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats.

Hepatology 2008 Dec;48(6):1913-23

Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy.

Decreased cardiac contractility and beta-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study beta-adrenergic-stimulated contractility and beta-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10(-10) to 10(-6) M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha-inhibiting subunit 2 (Galpha(i2)), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of Galpha(i2), PDE2a, and RGS2 down-regulates the beta-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy.
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http://dx.doi.org/10.1002/hep.22533DOI Listing
December 2008

Acute mountain sickness in a subject with metabolic syndrome at high altitude.

High Alt Med Biol 2008 ;9(3):245-8

Department of Clinical and Experimental Medicine, University of Padova, Italy.

Visitors at high altitude are increasing in age and comorbidities, which can lead to a failure in acclimatization. We describe the development of acute mountain sickness (AMS) in a 44-year-old man with metabolic syndrome and the time- and altitude-dependent correlation between the development of AMS and blood pressure and heart rate changes. Our observations support a dominant role of endothelial dysfunction in the pathogenesis of AMS and suggest new behavioral indications.
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http://dx.doi.org/10.1089/ham.2007.1075DOI Listing
January 2009

Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by modulating reactive oxygen species production and the Src/epidermal growth factor receptor/Akt signaling pathway.

J Nutr 2008 Sep;138(9):1596-601

Department of Clinical and Experimental Medicine and Experimental Biomedical Sciences, University of Padova, 35128 Padova, Italy.

We previously documented a clear-cut antihypertensive effect of green teat extract (GTE), which was associated with correction of endothelial dysfunction and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)-dependent model of hypertension, but the molecular mechanisms remain to be defined. As several effects of Ang II involve production of reactive oxygen species (ROS) and activation of 2nd messengers, such as mitogen-activated protein kinase (MAPK) and Akt, we investigated the effect of GTE on these signal transduction pathways in Ang II-treated rats. Rats were treated for 2 wk with Ang II infusion (700 mug.kg(-1).d(-1); n = 6, via osmotic minipumps), Ang II plus GTE (6 g/L) dissolved in the drinking water; n = 6), or vehicle (n = 6) to serve as controls. Blood pressure was monitored by telemetry throughout the study. The activation and expression of NAD(P)H oxidase subunits, protein kinase C isoforms, Src, epidermal growth factor receptor (EGFR), Akt, and MAPK were determined in the heart in vitro through immunoprecipitation and western blot analysis with specific antibodies. NAD(P)H oxidase enzymatic activity was measured by cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of the NAD(P)H oxidase subunit gp91(phox) and the translocation of Rac-1, as well as NAD(P)H oxidase enzymatic activity. Furthermore, it specifically reduced Ang II-induced Src, EGFR, and Akt phosphorylation. These results show that GTE blunts Ang II-induced cardiac hypertrophy specifically by regulating ROS production and the Src/EGFR/Akt signaling pathway activated by Ang II.
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http://dx.doi.org/10.1093/jn/138.9.1596DOI Listing
September 2008

Nifedipine versus carvedilol in the treatment of de novo arterial hypertension after liver transplantation: results of a controlled clinical trial.

Liver Transpl 2008 Jul;14(7):1020-8

Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

The aim of this study was to compare nifedipine and carvedilol in the treatment of de novo arterial hypertension after orthotopic liver transplantation (OLT). The study included 50 patients who developed arterial hypertension after OLT. Twenty-five patients received nifedipine (group A), and 25 received carvedilol (group B). Patients were defined as intolerant to nifedipine or carvedilol if severe adverse effects developed. These patients stopped the first drug and were switched to the other one. Patients were defined as full responders to monotherapy if there was normalization of blood pressure, and they were defined as partial responders by the need to add a second antihypertensive drug, ramipril. The 2 groups of patients were similar for baseline conditions. At the end of the study, patients intolerant to monotherapy were 48% of group A and 12.5% of group B (P < 0.01). Full responders were 20% of group A and 33.33% of group B (P < 0.01). Partial responders were 22% of group A and 54.1% of group B (P < 0.01). The addition of ramipril normalized blood pressure in 19% of partial responders to monotherapy (75% in partial responders to nifedipine and 30% in partial responders to carvedilol, P < 0.01). In responders to either monotherapy or combined therapy, there was a significant improvement of renal function. In responders to carvedilol, but not in responders to nifedipine, the daily dose of tacrolimus at 1 year should be reduced to 50% compared to the baseline dose to maintain the blood trough level in the therapeutic range.
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http://dx.doi.org/10.1002/lt.21442DOI Listing
July 2008

Silencing regulator of G protein signaling-2 (RGS-2) increases angiotensin II signaling: insights into hypertension from findings in Bartter's/Gitelman's syndromes.

J Hypertens 2008 May;26(5):938-45

Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Padova, Italy.

Objective: Regulator of G-protein signaling (RGS)-2 is a regulator of angiotensin II (Ang II) signaling. In Bartter's syndrome/Gitelman's syndrome (BS/GS), we have demonstrated increased RGS-2 levels and blunted Ang II signaling which contribute to their reduced vasomotor tone and remodeling. The present study investigates the effect of silencing RGS-2 in fibroblasts from six BS/GS patients on intracellular Ca2+ (CaI2+) mobilization and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, established Ang II-mediated responses.

Methods: Fibroblasts were RGS-2 silenced by transfecting chemically synthesized small interfering RNA. Silencing efficiency and Ang II-induced ERK 1/2 phosphorylation were evaluated by western blot and Ang II-induced Cai2+ using Fura-2 AM.

Results: RGS-2 expression in not silenced BS/GS fibroblasts from patients is increased compared with healthy controls [0.34 +/- 0.02 vs. 0.19 +/- 0.01 densitometric units (d.u.), P = 0.0005]. Silencing RGS-2 in BS/GS patients was achieved to the level of controls. Ang II-induced Cai2+ release and ERK 1/2 phosphorylation were reduced in not silenced cells from BG/GS patients compared with controls (112.16 +/- 13.2 vs. 130.33 +/- 13.64 mmol/l, P = 0.011 and 0.64 +/- 0.08 vs. 0.91 +/- 0.03 mmol/l, P < 0.006, respectively). Silencing RGS-2 in BS/GS patients increased Ang II-induced Cai2+ release and ERK 1/2 phosphorylation in silenced cells compared with not silenced cells [59.3 +/- 10.8 (peak-basal) vs. 40.5 +/- 14.1 nmol/l, P = 0.017 and 0.84 +/- 0.06 vs. 0.64 +/- 0.08 nmol/l, P < 0.03, respectively], whereas they were not different compared with controls (60.1 +/- 4.3 and 0.91 +/- 0.03 nmol/l). Integrating the Cai2+ response over time showed increased Cai2+ area under the curve (AUC) of BS/GS silenced cells compared with that of not silenced cells (P = 0.013).

Conclusion: This is the first report of silencing RGS-2 effect on Ang II signaling in a human clinical condition of altered vascular tone regulation and remodeling and establishes RGS-2 as a key regulatory element of Ang II signaling in humans.
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http://dx.doi.org/10.1097/HJH.0b013e3282f60d98DOI Listing
May 2008
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