title: Modulation of urinary peptidome in humans exposed to high altitude hypoxia.
abstract: The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia and to evaluate pharmacological approaches potentially useful as a therapy for chronic diseases related to hypoxia. We explored the urinary peptidome to detect alterations induced by the exposure of subjects to different altitudes (sea level, high altitude = 3500 m, very high altitude = 5400 m) and to pharmacological treatment. Urine samples were collected from 47 subjects, randomly and blindly assigned to placebo (n = 24) or Telmisartan (n = 23). Samples were purified by the use of magnetic beads, then analysed by MALDI-TOF MS. Results showed that the urinary peptidome is not affected by the administration of Telmisartan, neither at the sea level nor at high and very high altitudes. In contrast, the urinary protein profiles are modified when subjects are exposed to high and very high altitudes, and we detected six peptides differentially expressed in hypobaric hypoxia at high or very high altitude compared to the sea level. Two of them were identified as fragments of the glycoprotein uromodulin and of the α1-antitrypsin. This is the first proteomic study showing that hypobaric hypoxia conditions affect the urinary peptidome.
authors.affiliation: Department of Experimental Medicine, PhD Biomedical Technologies, Clinical Proteomics Unit, Università degli Studi di Milano-Bicocca, University of Milano-Bicocca, Via Cadore 48, 20900 Monza (MB), Italy. veronica.mainini@unimib.it
authors.forename: Veronica
authors.initials: V
authors.lastname: Mainini
authors.forename: Erica
authors.initials: E
authors.lastname: Gianazza
authors.forename: Clizia
authors.initials: C
authors.lastname: Chinello
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bilo
authors.forename: Miriam
authors.initials: M
authors.lastname: Revera
authors.forename: Andrea
authors.initials: A
authors.lastname: Giuliano
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caldara
authors.forename: Carolina
authors.initials: C
authors.lastname: Lombardi
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
authors.forename: Fulvio
authors.initials: F
authors.lastname: Magni
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
mesh_terms: D000328:Adult; D000531:Altitude; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000302:isolation & purification / Q000652:urine*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D000077333:Telmisartan; D044465:White People
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D010455:Peptides; D020543:Proteome; D000077333:Telmisartan