title: Increased Serum Levels of the Notch Ligand DLL1 are Associated with Diastolic Dysfunction, Reduced Exercise Capacity, and Adverse Outcome in Chronic Heart Failure.
abstract: BACKGROUND
  Notch receptors and ligands have been demonstrated in myocardial tissue in experimental as well as clinical heart failure (HF), and a role for Notch signaling in myocardial remodeling and disease progression may be anticipated. We hypothesized that serum levels of the Notch ligand Delta-like-1 (DLL1) would be associated with clinical and hemodynamic variables in patients with HF.
  
  
  RESULTS
  We measured serum DLL1 in 183 patients with chronic HF and 50 age- and sex-matched healthy control subjects by means of enzyme immunoassay. Our main findings were that (i) HF patients had significantly higher serum DLL1 levels than healthy control subjects, (ii) DLL1 levels were significantly correlated with neurohormonal activation, systemic inflammation, and impaired kidney function, (iii) high DLL1 levels were associated with diastolic dysfunction and reduced exercise capacity, but not with impaired systolic function, and (iv) in univariate analysis, but not after multivariable adjustment, high levels of DDL1 were associated with adverse outcome.
  
  
  CONCLUSIONS
  Our findings may imply that DLL1 and the Notch signaling pathways are involved in the pathophysiology of HF, potentially affecting diastolic function.
authors.affiliation: Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Anaesthesiology, Divison of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address: hnorum@ous-hf.no.
authors.forename: Hilde M
authors.initials: HM
authors.lastname: Norum
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K. G. Jebsen Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Aurelija
authors.initials: A
authors.lastname: Abraityte
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K. G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K. G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins; D003971:Diastole / Q000502:physiology*; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: Chronic heart failure; DLL1; Notch signaling; adverse outcome; diastolic dysfunction; exercise capacity