title: Extracellular vesicle protein CD14 relates to common carotid intima-media thickness in eight-year-old children.
abstract: BACKGROUND
  Atherosclerosis is a process that begins in childhood, develops over decades and underlies the majority of cardiovascular events in adulthood. Previously, we demonstrated in adults with cardiovascular disease that levels of extracellular vesicle (EV) proteins CD14, Serpin F2 and cystatin C predict vascular outcome. Here, we study for the first time whether these EV proteins are related to vascular characteristics in healthy, young children.
  
  
  RESULTS
  In 141 eight-year old children of the Wheezing-Illnesses-Studie-LEidsche-Rijn birth cohort, anthropometrics and blood pressure were measured. In addition, common carotid intima-media thickness, carotid distensibility and carotid Young's elastic modulus were obtained non-invasively using ultrasound imaging. A fasting lipid spectrum was obtained and EVs were isolated from plasma. Levels of EV proteins CD14, Serpin F2 and cystatin C were measured using a multiplex assay. In a multivariable linear regression model we assessed the relation between these EV proteins and the selected vascular characteristics. Of the studied EV proteins, CD14 levels were positively related to common carotid intima-media thickness (log transformed, beta = 7.31 ln(mm)/(ng/mg) (1.24, 13.38), p = 0.02). EV proteins Serpin F2 and cystatin C were not related to common carotid intima-media thickness. In addition, we found no relation between all three EV proteins and carotid distensibility or carotid Young's elastic modulus.
  
  
  CONCLUSIONS
  In healthy eight-year old children, extracellular vesicle protein CD14 levels seem positively related to common carotid intima-media thickness. This would point towards inflammatory vascular alterations inflicted by extracellular vesicle protein CD14 already in early life and warrants further investigation.
authors.affiliation: Department of Radiology, E.01.132, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: a.l.m.eikendal@umcutrecht.nl.
authors.forename: Anouk L M
authors.initials: AL
authors.lastname: Eikendal
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands; Laboratory of Experimental Cardiology, G02.523, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: H.M.denRuijter-2@umcutrecht.nl.
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Electronic address: cuiterwa@umcutrecht.nl.
authors.forename: Cuno S P M
authors.initials: CS
authors.lastname: Uiterwaal
authors.affiliation: Laboratory of Experimental Cardiology, G02.523, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: G.Pasterkamp@umcutrecht.nl.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Laboratory of Experimental Cardiology, G02.523, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: I.Hoefer@umcutrecht.nl.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Laboratory of Experimental Cardiology, G02.523, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Surgery, National University Singapore & Cardiovascular Research Institute, National University Health System, Singapore. Electronic address: surdvp@nus.edu.sg.
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.affiliation: Laboratory of Experimental Cardiology, G02.523, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: A.Schoneveld@umcutrecht.nl.
authors.forename: Arjan H
authors.initials: AH
authors.lastname: Schoneveld
authors.affiliation: Department of Radiology, E.01.132, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: T.Leiner@umcutrecht.nl.
authors.forename: Tim
authors.initials: T
authors.lastname: Leiner
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Electronic address: M.L.Bots@umcutrecht.nl.
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands; Department of Internal Medicine, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: F.L.J.Visseren@umcutrecht.nl.
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Electronic address: A.M.V.Evelein@umcutrecht.nl.
authors.forename: Annemieke M V
authors.initials: AM
authors.lastname: Evelein
mesh_terms: D017668:Age of Onset; D000886:Anthropometry; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology* / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D017536:Carotid Artery, Common / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D002648:Child; D055316:Cystatin C / Q000097:blood; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D012135:Respiratory Sounds; D059289:Vascular Stiffness; D014657:Vasculitis / Q000097:blood / Q000453:epidemiology* / Q000473:pathology; D000979:alpha-2-Antiplasmin / Q000032:analysis
chemical_list: D001786:Blood Glucose; C525030:CST3 protein, human; D055316:Cystatin C; D007328:Insulin; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D000979:alpha-2-Antiplasmin
keywords: Atherosclerosis; Children; Extracellular vesicle; Inflammation; Protein; Vascular alterations