title: Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort.
abstract: BACKGROUND
  SerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14-levels and the occurrence of acute heart failure in patients.
  
  
  RESULTS
  Extracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL- and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL-fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction.
  
  
  CONCLUSIONS
  Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events.
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.
authors.forename: Flora
authors.initials: F
authors.lastname: Vernooij
authors.affiliation: Department of Emergency Medicine, National University Health System, Singapore, Singapore.
authors.forename: Irwani
authors.initials: I
authors.lastname: Ibrahim
authors.affiliation: Department of Emergency Medicine, National University Health System, Singapore, Singapore.
authors.forename: Shirley
authors.initials: S
authors.lastname: Ooi
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Crystel M
authors.initials: CM
authors.lastname: Gijsberts
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Arjan H
authors.initials: AH
authors.lastname: Schoneveld
authors.affiliation: Department of Emergency Medicine, National University Health System, Singapore, Singapore.
authors.forename: Kuan Win
authors.initials: KW
authors.lastname: Sen
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Timmers
authors.affiliation: Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.|Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.
authors.forename: Chun Tzen
authors.initials: CT
authors.lastname: Jong
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mazlan
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.
authors.forename: Jiong-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: National Heart Centre Singapore, Singapore General Hospital, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cardiovascular Research Institute, National University Heart Centre Singapore; National University Health System Singapore, Singapore, Singapore.|Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D003174:Complement C1 Inactivator Proteins / Q000032:analysis*; D050718:Complement C1 Inhibitor Protein; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000032:analysis / Q000097:blood*; D000067128:Extracellular Vesicles / Q000473:pathology*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000473:pathology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000979:alpha-2-Antiplasmin / Q000032:analysis*
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D055316:Cystatin C; D018950:Lipopolysaccharide Receptors; C534949:SERPINF2 protein, human; C469952:SERPING1 protein, human; D000979:alpha-2-Antiplasmin
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