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

Article Article scientifique Article Receptor activator of NF- κB ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability eng 2012 author Quercioli Alessandra 688235 author Mach François 27365 author Bertolotto Maria author Lenglet Sébastien 589285 author Vuilleumier Nicolas 61406 author Galan Katia 123632 author Pagano Sabrina 0000-0001-7075-1182 758239 author Braunersreuther Vincent 510607 author Pelli Graziano 105578 author Pistoia Vito author Bianchi Le Henanf Giovanna 33355 author Cittadini Giuseppe author Viviani Giorgio Luciano author Pende Aldo author Roux-Lombard Pascale 22481 author Thomas Aurélien 647674 author Staub Christian 59634 author Ratib Osman 28848 author Dallegri Franco author Schindler Thomas 662511 author Montecucco Fabrizio 651324 124-139 10.1160/TH11-05-0324 22116393 0340-6245 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 Dewey 614.1 Dewey 616 Dewey 616.0757 Dewey 576 136 Département de biologie structurale et bioinformatique 21E 56 Département de médecine 221 62 Département de radiologie et informatique médicale 227 67 Institut de médecine légale 22A2 false 211 Auto-immunité, inflammation et athérosclérose 270 449 Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles 779 325 Athérosclérose 591 Thrombosis and haemostasis 107 1 cdf2b79b-1f57-4ab7-8245-86a4363dd4a2 Article (Published version) Restricted Quercioli A. - Thromb Haemost- 2012.pdf 741085 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de biologie structurale et bioinformatique Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine légale

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Receptor activator of NF- κB ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability	Thrombosis and haemostasis	2012	800	0
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Bianchi Le Henanf, Giovanna

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