title: Statin treatment is associated with reduction in serum levels of receptor activator of NF-κB ligand and neutrophil activation in patients with severe carotid stenosis.
abstract: Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Quercioli
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Fabre
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Katia
authors.identifier: 0000-0003-3299-6183
authors.initials: K
authors.lastname: Galan
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.affiliation: Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Nencioni
authors.affiliation: Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Inga
authors.identifier: 0000-0002-0112-0712
authors.initials: I
authors.lastname: Bauer
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Aldo
authors.identifier: 0000-0002-3804-918X
authors.initials: A
authors.lastname: Pende
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: Magaly
authors.initials: M
authors.lastname: Python
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bertolotto
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, San Martino Hospital, 10 Largo Rosanna Benzi, 16132 Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinella
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, San Martino Hospital, 10 Largo Rosanna Benzi, 16132 Genoa, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: Pane
authors.affiliation: Vascular and Endovascular Surgery Unit, Department of Surgery, San Martino Hospital, 10 Largo Rosanna Benzi, 16132 Genoa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Foundation for Medical Researches, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland ; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 16132 Genoa, Italy ; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland.
authors.forename: Fabrizio
authors.identifier: 0000-0003-0823-8729
authors.initials: F
authors.lastname: Montecucco
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy; D000069059:Atorvastatin; D016893:Carotid Stenosis / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D053245:RANK Ligand / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D053244:Osteoprotegerin; D011743:Pyrimidines; D011758:Pyrroles; D053245:RANK Ligand; D012333:RNA, Messenger; C506895:SPP1 protein, human; D013449:Sulfonamides; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D053495:Osteopontin; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9