Hilde M Norum1, Lars Gullestad2, Aurelija Abraityte3, Kaspar Broch4, Svend Aakhus4, Pål Aukrust5, Thor Ueland6. 1. 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. 2. 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. 3. Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 4. Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 5. 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. 6. 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.
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. METHODS AND 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.
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. METHODS AND 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: Hilde M Norum; Kaspar Broch; Annika E Michelsen; Ida G Lunde; Tove Lekva; Aurelija Abraityte; Christen P Dahl; Arnt E Fiane; Arne K Andreassen; Geir Christensen; Svend Aakhus; Pål Aukrust; Lars Gullestad; Thor Ueland Journal: J Cardiovasc Transl Res Date: 2017-05-04 Impact factor: 4.132
Authors: Aurelija Abraityte; Leif E Vinge; Erik T Askevold; Tove Lekva; Annika E Michelsen; Trine Ranheim; Katrine Alfsnes; Arnt Fiane; Svend Aakhus; Ida G Lunde; Christen P Dahl; Pål Aukrust; Geir Christensen; Lars Gullestad; Arne Yndestad; Thor Ueland Journal: J Mol Med (Berl) Date: 2017-03-30 Impact factor: 4.599
Authors: Negar Shahini; Annika E Michelsen; Per H Nilsson; Karin Ekholt; Lars Gullestad; Kaspar Broch; Christen P Dahl; Pål Aukrust; Thor Ueland; Tom Eirik Mollnes; Arne Yndestad; Mieke C Louwe Journal: Sci Rep Date: 2017-02-14 Impact factor: 4.379
Authors: Dagmar Hildebrand; Sebastian O Decker; Christian Koch; Felix C F Schmitt; Sophie Ruhrmann; Emmanuel Schneck; Michael Sander; Markus Alexander Weigand; Thorsten Brenner; Klaus Heeg; Florian Uhle Journal: Front Cell Infect Microbiol Date: 2019-07-23 Impact factor: 5.293