Receptor activator of NF-kappa B ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability
| Autor: | Alessandra Quercioli, Fabrizio Montecucco, Nicolas Vuilleumier, Thomas H. Schindler, Osman Ratib, Aurélien Thomas, Franco Dallegri, Vincent Braunersreuther, Maria Bertolotto, Giuseppe Cittadini, Sébastien Lenglet, François Mach, Christian Staub, Graziano Pelli, Giovanna Bianchi, Vito Pistoia, Katia Galan, Aldo Pende, Sabrina Pagano, Giorgio Luciano Viviani, Pascale Roux-Lombard |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Neutrophils Coronary Vessels/metabolism 030204 cardiovascular system & hematology Matrix metalloproteinase Cohort Studies chemistry.chemical_compound Matrix Metalloproteinase 8/metabolism 0302 clinical medicine Leukocytes Receptor ddc:616 biology Reverse Transcriptase Polymerase Chain Reaction Calcinosis Hematology Middle Aged RANK Ligand/metabolism Coronary Vessels 3. Good health Matrix Metalloproteinase 8 Matrix Metalloproteinase 9 Cardiovascular Diseases RANKL Leukocytes/metabolism Female Matrix Metalloproteinase 9/metabolism Reverse Transcriptase Polymerase Chain Reaction/methods Intracellular Adult musculoskeletal diseases medicine.medical_specialty Calcium/metabolism ddc:616.0757 03 medical and health sciences Internal medicine Cardiovascular Diseases/blood/metabolism medicine Humans Neutrophils/metabolism Protein kinase B PI3K/AKT/mTOR pathway Inflammation 030203 arthritis & rheumatology business.industry Activator (genetics) ddc:614.1 RANK Ligand NF-κB Endocrinology chemistry biology.protein Calcium business |
| Zdroj: | Thrombosis and Haemostasis; Vol 107 Thrombosis and Haemostasis Thrombosis and Haemostasis, Vol. 107, No 1 (2012) pp. 124-39 Thrombosis and haemostasis |
| ISSN: | 0340-6245 |
| DOI: | 10.1160/TH11-05-0324 |
| Popis: | SummaryThe “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. |
| Databáze: | OpenAIRE |
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