title: Metabolomic study of carotid-femoral pulse-wave velocity in women.
abstract: OBJECTIVE
  Carotid-femoral pulse-wave velocity (PWV) is a measure of aortic stiffness that is strongly associated with increased risk of cardiovascular morbidity and mortality. The aim of the current study was to identify the molecular markers and the pathways involved in differences in PWV in women, in order to further understand the regulation of arterial stiffening.
  
  
  METHODS
  A total of 280 known metabolites were measured in 1797 female twins (age range: 18-84 years) not on any antihypertensive medication. Metabolites associated with PWV (after adjustment for age, BMI, metabolite batch, and family relatedness) were entered into a backward linear regression. Transcriptomic analyses were further performed on the top compounds identified.
  
  
  RESULTS
  Twelve metabolites were associated with PWV (P < 1.8 × 10). One of the most strongly associated metabolites was uridine, which was not associated with blood pressure (BP) and traditional risk factors but correlated significantly with the gene-expression levels of the purinergic receptor P2RY2 (Beta = -0.010, SE = 0.003, P = 0.007), suggesting that it may play a role in regulating endothelial nitric oxide synthase phosphorylation. On the other hand, phenylacetylglutamine was strongly associated with both PWV and BP.
  
  
  CONCLUSIONS
  Circulating levels of uridine, phenylacetylglutamine, and serine appear strongly correlated with PWV in women.
authors.affiliation: aDepartment of Twin Research and Genetic Epidemiology bDepartment of Clinical Pharmacology, King's College London, London, UK cPfizer Worldwide Research and Development, Cambridge, Massachusetts dEdison Pharmaceuticals, Mountain View, California eMetabalon, Inc., Durham, North Carolina, USA fInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow gAcademic Rheumatology, University of Nottingham, Nottingham, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Marina
authors.initials: M
authors.lastname: Cecelja
authors.forename: Maria
authors.initials: M
authors.lastname: Psatha
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Brosnan
authors.forename: Jeff
authors.initials: J
authors.lastname: Trimmer
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.forename: Phil
authors.initials: P
authors.lastname: Chowienczyk
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism*; D001158:Arteries; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D005260:Female; D006801:Humans; D055432:Metabolomics; D008875:Middle Aged; D063177:Pulse Wave Analysis; D012307:Risk Factors; D059289:Vascular Stiffness; D055815:Young Adult
chemical_list: D000596:Amino Acids; D015415:Biomarkers