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

Hilde M Norum1,2,3, Kaspar Broch4, Annika E Michelsen5,6

  • 1Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. hnorum@rr-research.no.

Journal of Cardiovascular Translational Research
|May 6, 2017
PubMed

Insights

Secreted Notch ligands, including Delta-like Notch ligand 1 (DLL1) and periostin (POSN), are elevated in severe dilated cardiomyopathy (DCM). These molecules show distinct associations with cardiac function, suggesting roles in DCM progression.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Biomarker Discovery

Background:

  • Adverse myocardial remodeling is a hallmark of dilated cardiomyopathy (DCM).
  • Notch signaling pathways are implicated in cardiac development and disease.
  • Dysregulation of secreted Notch ligands may contribute to DCM pathogenesis.

Purpose of the Study:

  • To investigate the plasma and myocardial expression levels of specific Notch ligands in patients with DCM.
  • To explore the association between these ligands and cardiac function and disease severity.

Main Methods:

  • Plasma levels of DLL1, DLK1, and POSN were measured in 102 DCM patients and 32 controls using quantitative assays.
  • Myocardial mRNA and protein expression of DLL1, DLK1, and POSN were analyzed in 25 explanted hearts from DCM patients.
  • Correlation analyses were performed to link ligand levels with clinical parameters and cardiac function indices.

Main Results:

  • Elevated plasma levels of DLL1 and POSN were observed in severe DCM patients.
  • Circulating DLL1 and POSN levels correlated with diastolic dysfunction severity.
  • Right ventricular tissue expression of DLL1 and DLK1 was associated with preserved cardiac function, while POSN expression correlated with deteriorated function.

Conclusions:

  • DLL1, DLK1, and POSN are dysregulated in end-stage DCM.
  • These ligands may play differential roles in mediating cardiac remodeling and function in DCM.
  • Further research is warranted to elucidate the precise mechanisms of these ligands in DCM progression.

Keywords:
Delta-like 1 homologue (DLK1)Delta-like Notch ligand 1 (DLL1)Diastolic dysfunctionDilated cardiomyopathyMyocardial remodelingNotch pathwayPeriostin (POSN)

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