Genomes and Genes
Affiliation: San Raffaele Scientific Institute
- Main results of the ouabain and adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxinJan A Staessen
The Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Research, University of Leuven, Leuven, Belgium
Trials 12:13. 2011..Rostafuroxin lowered blood pressure (BP) in some animal models and in humans...
- A new antihypertensive agent that antagonizes the prohypertensive effect of endogenous ouabain and adducinPaolo Manunta
Division of Nephrology, Dialysis and Hypertension, University Vita Salute San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy
Cardiovasc Hematol Agents Med Chem 4:61-6. 2006..In conclusion, PST2238, because of its peculiar action mechanism, represents a new tool to disentangle the complex relationship between salt intake, genetic control of renal sodium handling and EO effect...
- Pharmacogenomics and pharmacogenetics of hypertension: update and perspectives--the adducin paradigmPaolo Manunta
Division of Nephrology, Dialysis, and Hypertension, University Vita Salute San Raffale, Via Olgettina 60, 20131 Milan, Italy
J Am Soc Nephrol 17:S30-5. 2006....
- Adducin polymorphisms and the treatment of hypertensionPaolo Manunta
Universita Vita Salute San Raffaele Hospital, Division of Nephrology, Dialysis and Hypertension, Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milan, Italy
Pharmacogenomics 8:465-72. 2007....
- Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertensionPaolo Manunta
Division of Nephrology, Dialysis and Hypertension, Scientific Institute San Raffaele, University Vita Salute San Raffaele, Milan, Italy
J Hypertens 26:914-20. 2008..The basolateral Na pump drives renotubular reabsorption. In cultured renal cells, mutant adducins, as well as sub-nanomolar ouabain concentrations, stimulate the Na-K pump...
- Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulationPaolo Manunta
Division of Nephrology, Dialysis, and Hypertension, University Vita Salute San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy
Hypertension 52:366-72. 2008..Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides...
- Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertensionP Manunta
Division of Nephrology, Dialysis, and Hypertension, University Vita Salute San Raffaele, Milan, Italy
Hypertension 38:198-203. 2001..Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone...
- Endogenous ouabain in cardiovascular function and diseasePaolo Manunta
San Raffaele Scientific Institute, Division of Nephrology, Dialysis, and Hypertension, Universita Vita Salute San Raffaele Hospital, Milan, Italy
J Hypertens 27:9-18. 2009..The outstanding analytical issues include the elucidation of distal events in the biosynthetic pathway for endogenous ouabain and identification of molecular mechanisms that regulate its secretion and clearance...
- Endogenous ouabain in renal Na(+) handling and related diseasesPaolo Manunta
Scientific Institute San Raffaele, Universita Vita Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy
Biochim Biophys Acta 1802:1214-8. 2010..Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis...
- Left ventricular mass, stroke volume, and ouabain-like factor in essential hypertensionP Manunta
University of Milan and Division of Nephrology, Dialysis and Hypertension, IRCCS San Raffaele Hospital, Milan, Italy
Hypertension 34:450-6. 1999..We propose that the OLF affects cardiovascular function and structure and should be considered as a factor that contributes to the risk of morbid events...
- Adducin polymorphism affects renal proximal tubule reabsorption in hypertensionP Manunta
Division of Nephrology, University of Milan, Italy
Hypertension 33:694-7. 1999..In conclusion, the adducin gene can be considered to be a 'renal hypertensive gene' that modulates the capacity of tubular epithelial cells to transport Na+ and hence contributes to the level of blood pressure...
- Endogenous ouabain and the renin-angiotensin-aldosterone system: distinct effects on Na handling and blood pressure in human hypertensionPaolo Manunta
Nephrology, and Dialysis San Raffaele Scientific Institute, Universita Vita Salute San Raffaele, Milan, Italy
J Hypertens 29:349-56. 2011..To evaluate whether the renin-angiotensin-aldosterone system (RAAS) and endogenous ouabain system differently affect renal Na handling and blood pressure...
- High circulating levels of endogenous ouabain in the offspring of hypertensive and normotensive individualsPaolo Manunta
Division of Nephrology, Dialysis and Hypertension, University Vita e Salute San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy
J Hypertens 23:1677-81. 2005..The aim of this study was to investigate whether these cardiac modifications are related to plasma EO levels in the offspring of hypertensive families...
- Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uraemic patientsL Soldati
Division of Nephrology, Dialysis and Hypertension, San Raffaele Scientific Institute, University of Milan, Italy
Nephrol Dial Transplant 16:85-90. 2001..Reduced resistance to PTH could contribute to this phenomenon...
- Hypertension in hemodialysis patientsM Querques
Operative Unit of Nephrology and Dialysis, Department of Nephrology, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Minerva Urol Nefrol 62:41-50. 2010....
- Endogenous ouabain and cardiomyopathy in dialysis patientsP Stella
Division of Nephrology, Dialysis, and Hypertension, University Vita e Salute, San Raffaele Hospital, Milan, Italy
J Intern Med 263:274-80. 2008..EO was measured by a specific radioimmunoassay and by mass spectrometry...
- Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertensionD Cusi
Postgraduate School of Nephrology, University of Milan, Italy
Lancet 349:1353-7. 1997..We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations...
- Adducin in essential hypertensionP Manunta
Postgraduate School of Nephrology, University of Milan and Division of Nephrology, Dialysis and Hypertension, S Raffaele Hospital, Italy
FEBS Lett 430:41-4. 1998..However adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied...
- Genetics of primary hypertension: the clinical impact of adducin polymorphismsLorena Citterio
San Raffaele Scientific Institute, Universita Vita Salute San Raffaele, Milan, Italy
Biochim Biophys Acta 1802:1285-98. 2010..The size of this impact is variable and affected by the context...
- Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabainGrazia Tripodi
Prassis Sigma Tau, Research Institute, Milan, Italy
Am J Hypertens 22:357-63. 2009..Furthermore, the renal excretion of cardiac glycosides is mediated by the organic anion transporter (SLCO4C1) at the basolateral membrane and the P-glycoprotein (PGP) (encoded by MDR1) at the apical membrane of the nephron...
- Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertensionCristina Barlassina
Department of Sciences and Biomedical Technologies, University of Milan, via Fantoli 16 15, 20090 Milan, Italy
Hum Mol Genet 16:1630-8. 2007..This study supports the candidacy of CLCNKA as a new susceptibility gene for salt-sensitivity...
- ACE and alpha-adducin polymorphism as markers of individual response to diuretic therapyMaria Teresa Sciarrone
Department of Nephrology and Graduate School of Nephrology Universita Vita e Salute, Milan, Italy
Hypertension 41:398-403. 2003....
- Role of the adducin family genes in human essential hypertensionChiara Lanzani
Division of Nephrology, Dialysis and Hypertension University Vita Salute, IRCCS San Raffaele Hospital, Milano, Italy
J Hypertens 23:543-9. 2005..Adducin functions within cells as a heterodimer composed of various combinations of three subunits that are coded by three genes (ADD1, 2, 3) each located on a different chromosome...
- alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathyMara Ferrandi
Prassis sigma tau Research Institute, Settimo Milanese, Milan, Italy
J Mol Med (Berl) 88:203-17. 2010..These findings suggest that adducin genetic variants participate in the development of glomerular lesions by modulating the expression of specific podocyte proteins...
- Endogenous ouabain in Ménière's diseaseRoberto Teggi
ENT Department, IRRCS San Raffaele, Milan, Italy
Otol Neurotol 31:153-6. 2010..Our purpose was to measure plasma levels of EO in Ménière's Disease (MD) subjects as a possible predisposing factor to developing and maintaining hydrops...
- Gly460Trp alpha-adducin mutation as a possible mechanism leading to endolymphatic hydrops in Ménière's syndromeRoberto Teggi
ENT Department, San Raffaele Scientific Institute, Vita Salute University San Raffaele, Milan, Italy
Otol Neurotol 29:824-8. 2008..ADD1 Gly460Trp polymorphism is associated with salt-sensitive hypertension and increased Na-K pump activity in transfected cells. This study aims to verify the role of adducin in the development of MD...
- Low-salt diet and diuretic effect on blood pressure and organ damagePaolo Manunta
Division of Nephrology, Dialysis and Hypertension, University Vita Salute San Raffaele Hospital, Milan, Italy
J Am Soc Nephrol 15:S43-6. 2004..These data support the notion that matching of the genetic mechanism with the drug mechanisms of action produces a clear therapeutic benefit...
- Genetics of essential hypertension: from families to genesCristina Barlassina
Division of Nephrology, Dyalisis and Hypertension, University Vita e Salute San Raffaele Hospital, Milan, Italy
J Am Soc Nephrol 13:S155-64. 2002..A negative finding or a minor genetic effect in a general population may become a major gene effect in a subset of people with the appropriate genetic and environmental backgrounds...
- The clinical pathway for hypertensive patient of local health unit, hospitals and general practitioners, the Milan experienceAlberto Donzelli
Service of Education for Appropriateness and Evidence Based Medicine Local Health Unit, ASL of Milan, Italy
Rev Recent Clin Trials 6:16-23. 2011....
- Targeting Ouabain- and Adducin-dependent mechanisms of hypertension and cardiovascular remodeling as a novel pharmacological approachPatrizia Ferrari
Prassis Istituto di Ricerche Sigma Tau, Settimo Milanese, Milano, Italy
Med Hypotheses 68:1307-14. 2007..Currently, a phase II multicenter European clinical trial is ongoing for providing the proof of concept that such a compound is effective in the subset of patients where these two mechanisms are at work...
- The endogenous ouabain: molecular basis of its role in hypertension and cardiovascular complicationsMara Ferrandi
Prassis sigma tau Research Institute, Settimo Milanese, 20019 Milan, Italy
Front Biosci 10:2472-7. 2005....
- Genotyping of essential hypertension single-nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primersChikh Bengra
Department of Pathology, The University of Virginia, PO Box 800214, Charlottesville, VA 22908, USA
Clin Chem 48:2131-40. 2002..A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management...
- OASIS-HT: design of a pharmacogenomic dose-finding studyJan A Staessen
Department of Molecular and Cardiovascular Research, Hypertension and Cardiovascular Rehabilitation Unit, Study Coordinating Centre, University of Leuven, Belgium
Pharmacogenomics 6:755-75. 2005..To our knowledge, OASIS-HT is the first Phase II dose-finding study in which a genetic hypothesis is driving primary and secondary end points...
- Adducin, renal intermediate phenotypes, and hypertensionGiuseppe Bianchi
Hypertension 44:394-5. 2004
- Are the new single nucleotide polymorphisms (SNPs) relevant for hypertensive populations?Paolo Manunta
J Hypertens 20:2335-6. 2002
- Salt, endogenous ouabain and blood pressure interactions in the general populationJi Guang Wang
Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement voor Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit Leuven, Leuven, Belgium
J Hypertens 21:1475-81. 2003..We investigated the distribution of plasma ouabain in the general population in relation to blood pressure and other determinants of sodium homeostasis...
- Association of atrial natriuretic peptide and type a natriuretic peptide receptor gene polymorphisms with left ventricular mass in human essential hypertensionSperanza Rubattu
IRCCS Neuromed, Polo Molisano University of Rome La Sapienza, Pozzilli, Italy
J Am Coll Cardiol 48:499-505. 2006....
- Angiotensin-converting enzyme I/D and alpha-adducin Gly460Trp polymorphisms: from angiotensin-converting enzyme activity to cardiovascular outcomeYan Li
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Research, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
Hypertension 49:1291-7. 2007....
- Na+, kidney, hypertension and genes: lessons from ratsGiuseppe Bianchi
J Hypertens 22:1461-4. 2004
- Different effects of marinobufagenin and endogenous ouabainPaolo Manunta
J Hypertens 22:257-9. 2004
- Association between arterial properties and renal sodium handling in a general populationJitka Seidlerova
Studies Coordination Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
Hypertension 48:609-15. 2006..These findings demonstrate that there might be an influence of renal sodium handling on arterial properties or vice versa or that common mechanisms might influence both arterial and renal function...
- Haplotype analysis in human hypertensionPaolo Manunta
J Hypertens 23:711-2. 2005
- Salt intake and depletion increase circulating levels of endogenous ouabain in normal menPaolo Manunta
Department of Physiology, University of Maryland School of Medicine, Baltimore, 655 West Baltimore St, Baltimore, Maryland 21201, USA
Am J Physiol Regul Integr Comp Physiol 290:R553-9. 2006..The dramatic impact of high-salt diets on plasma EO is consistent with its proposed role as a humoral vasoconstrictor that links salt intake with vascular function in hypertension...
- Independent and incremental prognostic value of endogenous ouabain in idiopathic dilated cardiomyopathyMaria Vittoria Pitzalis
Institute of Cardiology, University of Bari, Bari, Italy
Eur J Heart Fail 8:179-86. 2006..This study provides the first evidence that circulating EO is a novel, independent and incremental marker that predicts the progression of heart failure...
- Ouabain and serum sodiumJerzy Gasowski
Hypertension 45:e16; author reply e16-7. 2005