Scientific article

Receptor activator of NF- κB ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability

Published inThrombosis and haemostasis, vol. 107, no. 1, p. 124-139
Publication date2012

The "blood vulnerability", resulting from the complex balance between serum molecules and inflammatory cell atherosclerotic activities, is a major determinant in the evaluation of the "global patient cardiovascular vulnerability". In the present study, we focused on the role of the soluble receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL, a potential marker of coronary calcification and vulnerability) in the release of neutrophilic proteases. Then, the association between these mediators and the degree of coronary calcification (assessed by coronary calcium score [CCS]) was investigated in 20 subjects (aged ≥65 years) asymptomatic for cardiovascular disease. Results showed that RANKL dose-dependently induced matrix metalloprotease (MMP)-8 and MMP-9 release from human primary neutrophils cultured in Teflon dishes (suspension condition, mimicking cells circulating in the blood stream). Conversely, when adherent to polystyrene, neutrophils became unresponsive to RANKL. RANKL did not influence the release of other neutrophilic products in suspension and adherence cultures as well as neutrophil migration. RANKL-induced release of MMPs was dependent on the activation of defined intracellular signalling pathways (PI3K/Akt and ERK1/2). In asymptomatic subjects, serum levels of RANKL, MMP-8 and MMP-9 positively correlated with CCS, reflecting a potential relationship between circulating RANKL and coronary calcification. In conclusion, RANKL increased the release of neutrophilic products potentially related to the "blood" vulnerability via defined intracellular pathways. Serum levels of RANKL might represent a potential biomarker of coronary calcification and related cardiovascular risk.

  • Adult
  • Calcinosis
  • Calcium/metabolism
  • Cardiovascular Diseases/blood/metabolism
  • Cohort Studies
  • Coronary Vessels/metabolism
  • Female
  • Humans
  • Inflammation
  • Leukocytes/metabolism
  • Male
  • Matrix Metalloproteinase 8/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Middle Aged
  • Neutrophils/metabolism
  • RANK Ligand/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction/methods
Citation (ISO format)
QUERCIOLI, Alessandra et al. Receptor activator of NF- κB ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability. In: Thrombosis and haemostasis, 2012, vol. 107, n° 1, p. 124–139. doi: 10.1160/TH11-05-0324
Main files (1)
Article (Published version)
ISSN of the journal0340-6245

Technical informations

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