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

Bertolotto, Maria
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Published in Thrombosis and haemostasis. 2012, vol. 107, no. 1, p. 124-39
Abstract 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.
Keywords AdultCalcinosisCalcium/metabolismCardiovascular Diseases/blood/metabolismCohort StudiesCoronary Vessels/metabolismFemaleHumansInflammationLeukocytes/metabolismMaleMatrix Metalloproteinase 8/metabolismMatrix Metalloproteinase 9/metabolismMiddle AgedNeutrophils/metabolismRANK Ligand/metabolismReverse Transcriptase Polymerase Chain Reaction/methods
PMID: 22116393
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Research groups Chimie et protéomique clinique (270)
Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles (779)
L'athérosclérose et ses complications cliniques (591)
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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. 124-39. doi: 10.1160/TH11-05-0324 https://archive-ouverte.unige.ch/unige:27586

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Deposited on : 2013-04-26

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