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

Alessandra Quercioli, François Mach, Maria Bertolotto, Sébastien Lenglet, Nicolas Vuilleumier, Katia Galan, Sabrina Pagano, Vincent Braunersreuther, Graziano Pelli, Vito Pistoia, Giovanna Bianchi, Giuseppe Cittadini, Giorgio Luciano Viviani, Aldo Pende, Pascale Roux-Lombard, Aurélien Thomas, Christian Staub, Osman Ratib, Franco Dallegri, Thomas Helmut SchindlerFabrizio Montecucco

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Summary The "blood vulnerability", resulting from the complex balance betweenserum molecules and inflammatory cell atherosclerotic activities, is amajor determinant in the evaluation of the "global patient cardiovascularvulnerability". In the present study, we focused on the role of the solublereceptor 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 betweenthese mediators and the degree of coronary calcification (assessed bycoronary calcium score [CCS]) was investigated in 20 subjects (aged≥65 years) asymptomatic for cardiovascular disease. Results showedthat RANKL dose-dependently induced matrix metalloprotease(MMP)-8 and MMP-9 release from human primary neutrophils culturedin Teflon dishes (suspension condition, mimicking cells circulating in theblood stream). Conversely, when adherent to polystyrene, neutrophilsbecame unresponsive to RANKL. RANKL did not influence the release ofother neutrophilic products in suspension and adherence cultures aswell as neutrophil migration. RANKL-induced release of MMPs was dependenton the activation of defined intracellular signalling pathways(PI3K/Akt and ERK1/2). In asymptomatic subjects, serum levels ofRANKL, MMP-8 and MMP-9 positively correlated with CCS, reflecting apotential relationship between circulating RANKL and coronary calcification.In conclusion, RANKL increased the release of neutrophilic productspotentially related to the "blood" vulnerability via defined intracellularpathways. Serum levels of RANKL might represent a potentialbiomarker of coronary calcification and related cardiovascular risk.

Original languageEnglish
Pages (from-to)124-139
Number of pages16
JournalThrombosis and Haemostasis
Volume107
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

RANK Ligand
Metalloproteases
Suspensions
Neutrophils
Calcium
Asymptomatic Diseases
NF-kappa B
Polystyrenes
Polytetrafluoroethylene
Serum
Matrix Metalloproteinases
Phosphatidylinositol 3-Kinases
Peptide Hydrolases
Cardiovascular Diseases
Ligands

Keywords

  • Atherosclerosis
  • Leukocyte function/activation
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Hematology

Cite this

Quercioli, A., Mach, F., Bertolotto, M., Lenglet, S., Vuilleumier, N., Galan, K., ... Montecucco, F. (2012). Receptor activator of NF-κB ligand (RANKL) increases the release ofneutrophil products associated with coronary vulnerability. Thrombosis and Haemostasis, 107(1), 124-139. https://doi.org/10.1160/TH11-05-0324

Receptor activator of NF-κB ligand (RANKL) increases the release ofneutrophil products associated with coronary vulnerability. / Quercioli, Alessandra; Mach, François; Bertolotto, Maria; Lenglet, Sébastien; Vuilleumier, Nicolas; Galan, Katia; Pagano, Sabrina; Braunersreuther, Vincent; Pelli, Graziano; Pistoia, Vito; Bianchi, Giovanna; Cittadini, Giuseppe; Viviani, Giorgio Luciano; Pende, Aldo; Roux-Lombard, Pascale; Thomas, Aurélien; Staub, Christian; Ratib, Osman; Dallegri, Franco; Schindler, Thomas Helmut; Montecucco, Fabrizio.

In: Thrombosis and Haemostasis, Vol. 107, No. 1, 01.2012, p. 124-139.

Research output: Contribution to journalArticle

Quercioli, A, Mach, F, Bertolotto, M, Lenglet, S, Vuilleumier, N, Galan, K, Pagano, S, Braunersreuther, V, Pelli, G, Pistoia, V, Bianchi, G, Cittadini, G, Viviani, GL, Pende, A, Roux-Lombard, P, Thomas, A, Staub, C, Ratib, O, Dallegri, F, Schindler, TH & Montecucco, F 2012, 'Receptor activator of NF-κB ligand (RANKL) increases the release ofneutrophil products associated with coronary vulnerability', Thrombosis and Haemostasis, vol. 107, no. 1, pp. 124-139. https://doi.org/10.1160/TH11-05-0324
Quercioli, Alessandra ; Mach, François ; Bertolotto, Maria ; Lenglet, Sébastien ; Vuilleumier, Nicolas ; Galan, Katia ; Pagano, Sabrina ; Braunersreuther, Vincent ; Pelli, Graziano ; Pistoia, Vito ; Bianchi, Giovanna ; Cittadini, Giuseppe ; Viviani, Giorgio Luciano ; Pende, Aldo ; Roux-Lombard, Pascale ; Thomas, Aurélien ; Staub, Christian ; Ratib, Osman ; Dallegri, Franco ; Schindler, Thomas Helmut ; Montecucco, Fabrizio. / Receptor activator of NF-κB ligand (RANKL) increases the release ofneutrophil products associated with coronary vulnerability. In: Thrombosis and Haemostasis. 2012 ; Vol. 107, No. 1. pp. 124-139.
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AU - Vuilleumier, Nicolas

AU - Galan, Katia

AU - Pagano, Sabrina

AU - Braunersreuther, Vincent

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AU - Pende, Aldo

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