Vittoria Matafora1, Chiara Lanzani2, Laura Zagato3, Paolo Manunta3, Miriam Zacchia4, Francesco Trepiccione4,5, Marco Simonini3, Giovambattista Capasso4,5, Angela Bachi6. 1. IFOM-FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy. 2. Chair of Nephrology, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Università Vita Salute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. lanzani.chiara@hsr.it. 3. Chair of Nephrology, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Università Vita Salute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. 4. Department of Translational Medical Science, University of Campania Luigi Vanvitelli, Naples, Italy. 5. Biogem S.c.a.r.l., Ariano Irpino, Italy. 6. IFOM-FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy. angela.bachi@ifom.eu.
Abstract
BACKGROUND: Hypertension is a complex disease and is the major cause of cardiovascular complications. In the vast majority of individuals, the aetiology of elevated blood pressure (BP) cannot be determined, thus impairing optimized therapies and prognosis for individual patients. A more precise understanding of the molecular pathogenesis of hypertension remains a pressing priority for both basic and translational research. Here we investigated the effect of salt on naive hypertensive patients in order to better understand the salt intake-blood pressure relationship. METHODS: Patients underwent an acute saline infusion and were defined as salt-sensitive or salt-resistant according to mean blood pressure changes. Urinary proteome changes during the salt load test were analysed by a label-free quantitative proteomics approach. RESULTS: Our data show that salt-sensitive patients display equal sodium reabsorption as salt-resistant patients, as major sodium transporters show the same behaviour during the salt load. However, salt-sensitive patients regulate the renin angiotensin system (RAS) differently from salt-resistant patients, and upregulate proteins, as epidermal growth factor (EGF) and plasminogen activator, urokinase (PLAU), involved in the regulation of epithelial sodium channel ENaC activity. CONCLUSIONS: Salt-sensitive and salt-resistant subjects have similar response to a saline/volume infusion as detected by urinary proteome. However, we identified glutamyl aminopeptidase (ENPEP), PLAU, EGF and Xaa-Pro aminopeptidase 2 precursor XPNPEP2 as key molecules of salt-sensitivity, through modulation of ENaC-dependent sodium reabsorption along the distal tubule.
BACKGROUND:Hypertension is a complex disease and is the major cause of cardiovascular complications. In the vast majority of individuals, the aetiology of elevated blood pressure (BP) cannot be determined, thus impairing optimized therapies and prognosis for individual patients. A more precise understanding of the molecular pathogenesis of hypertension remains a pressing priority for both basic and translational research. Here we investigated the effect of salt on naive hypertensivepatients in order to better understand the salt intake-blood pressure relationship. METHODS:Patients underwent an acute saline infusion and were defined as salt-sensitive or salt-resistant according to mean blood pressure changes. Urinary proteome changes during the salt load test were analysed by a label-free quantitative proteomics approach. RESULTS: Our data show that salt-sensitive patients display equal sodium reabsorption as salt-resistant patients, as major sodium transporters show the same behaviour during the salt load. However, salt-sensitive patients regulate the renin angiotensin system (RAS) differently from salt-resistant patients, and upregulate proteins, as epidermal growth factor (EGF) and plasminogen activator, urokinase (PLAU), involved in the regulation of epithelial sodium channel ENaC activity. CONCLUSIONS:Salt-sensitive and salt-resistant subjects have similar response to a saline/volume infusion as detected by urinary proteome. However, we identified glutamyl aminopeptidase (ENPEP), PLAU, EGF and Xaa-Pro aminopeptidase 2 precursor XPNPEP2 as key molecules of salt-sensitivity, through modulation of ENaC-dependent sodium reabsorption along the distal tubule.
Authors: Paolo Manunta; Gail Lavery; Chiara Lanzani; Peter S Braund; Marco Simonini; Claire Bodycote; Laura Zagato; Simona Delli Carpini; Cristina Tantardini; Elena Brioni; Giuseppe Bianchi; Nilesh J Samani Journal: Hypertension Date: 2008-06-30 Impact factor: 10.190