The Notch Ligands DLL1 and Periostin Are Associated with Symptom Severity and Diastolic Function in Dilated Cardiomyopathy

  • 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
Original Article

DOI: 10.1007/s12265-017-9748-y

Cite this article as:
Norum, H.M., Broch, K., Michelsen, A.E. et al. J. of Cardiovasc. Trans. Res. (2017). doi:10.1007/s12265-017-9748-y
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Abstract

In dilated cardiomyopathy (DCM), adverse myocardial remodeling is essential, potentially involving Notch signaling. We hypothesized that secreted Notch ligands would be dysregulated in DCM. We measured plasma levels of the canonical Delta-like Notch ligand 1 (DLL1) and non-canonical Notch ligands Delta-like 1 homologue (DLK1) and periostin (POSN) in 102 DCM patients and 32 matched controls. Myocardial mRNA and protein levels of DLL1, DLK1, and POSN were measured in 25 explanted hearts. Our main findings were: (i) Circulating levels of DLL1 and POSN were higher in patients with severe DCM and correlated with the degree of diastolic dysfunction and (ii) right ventricular tissue expressions of DLL1, DLK1, and POSN were oppositely associated with cardiac function indices, as high DLL1 and DLK1 expression corresponded to more preserved and high POSN expression to more deteriorated cardiac function. DLL1, DLK1, and POSN are dysregulated in end-stage DCM, possibly mediating different effects on cardiac function.

Keywords

Dilated cardiomyopathy Diastolic dysfunction Delta-like Notch ligand 1 (DLL1) Delta-like 1 homologue (DLK1) Periostin (POSN) Notch pathway Myocardial remodeling 

Abbreviations

DCM

Dilated cardiomyopathy

DLL1

Delta-like Notch ligand 1

DLK1

Delta-like 1 homologue

POSN

Periostin

HF

Heart failure

ECM

Extracellular matrix

HFrEF

Heart failure with reduced ejection fraction

NYHA

New York Heart Association

LV

Left ventricle

RV

Right ventricle

Supplementary material

12265_2017_9748_MOESM1_ESM.docx (27 kb)
ESM 1(DOCX 27 kb)

Funding information

Funder NameGrant NumberFunding Note
The Raagholt Foundation
    The Norwegian Order of Odd Fellows

      Copyright information

      © Springer Science+Business Media New York 2017

      Authors and Affiliations

      • Hilde M. Norum
        • 1
        • 2
        • 3
      • Kaspar Broch
        • 4
      • Annika E. Michelsen
        • 1
        • 2
      • Ida G. Lunde
        • 5
        • 6
      • Tove Lekva
        • 1
      • Aurelija Abraityte
        • 1
        • 2
        • 5
      • Christen P. Dahl
        • 1
        • 4
        • 5
      • Arnt E. Fiane
        • 7
      • Arne K. Andreassen
        • 4
      • Geir Christensen
        • 5
        • 6
      • Svend Aakhus
        • 4
        • 8
      • Pål Aukrust
        • 1
        • 2
        • 9
        • 10
        • 11
      • Lars Gullestad
        • 2
        • 4
      • Thor Ueland
        • 1
        • 2
        • 11
      1. 1.Research Institute of Internal MedicineOslo University HospitalOsloNorway
      2. 2.Faculty of MedicineUniversity of OsloOsloNorway
      3. 3.Department of Research and Development, Division of Emergencies and Critical CareOslo University HospitalOsloNorway
      4. 4.Department of CardiologyOslo University HospitalOsloNorway
      5. 5.Center for Heart Failure ResearchUniversity of OsloOsloNorway
      6. 6.Institute for Experimental Medical ResearchOslo University Hospital, UllevålOsloNorway
      7. 7.Department of Cardiothoracic SurgeryOslo University HospitalOsloNorway
      8. 8.Department of Circulation and Imaging, Faculty of MedicineNorwegian University of Science and TechnologyTrondheimNorway
      9. 9.Section of Clinical Immunology and Infectious DiseasesOslo University HospitalOsloNorway
      10. 10.K.G. Jebsen Inflammation Research CenterUniversity of OsloOsloNorway
      11. 11.K.G. Jebsen Thrombosis Research and Expertise CenterUniversity of TromsøTromsøNorway

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