title: Quantitative proteomics reveals novel therapeutic and diagnostic markers in hypertension.
abstract: Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension.
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Milan, Italy ; Chair of Nephrology, Department of Cardio-Vascular Medicine, Second University of Naples, Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Matafora
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zagato
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Ferrandi
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Molinari
authors.affiliation: Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Casamassima
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Delli Carpini
authors.affiliation: Chair of Nephrology, Department of Cardio-Vascular Medicine, Second University of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trepiccione
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milan, Italy ; Chair of Nephrology, University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.affiliation: Chair of Nephrology, Department of Cardio-Vascular Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
keywords: BMI, body mass index; BP, blood pressure; DBP, diastolic BP; GO, Gene Ontology; Glomerular injury; LC–MS/MS, liquid chromatography coupled to tandem mass spectrometry; MBP, mean BP.; MQ, MaxQuant; Nephrinuria; Quantitative proteomics; SBP, systolic BP; SR, salt resistant; SS, salt sensitive; Salt homeostasis; Salt sensitive hypertension; Urinary biomarker; Uromodulin