title: Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease-related vascular calcification.
abstract: BACKGROUND
  Vascular calcification, a regulated process in chronic kidney disease (CKD), requires vascular smooth muscle cell (VSMC) differentiation into osteoblast-like cells. This phenomenon can be enhanced by inflammatory cytokines and production of reactive oxygen species (ROS). In CKD rats with vascular calcification, we investigated whether inflammatory cytokines, ROS generation, and downstream signaling events are associated with CKD-related vascular calcification.
  
  
  METHODS
  CKD was induced in male Wistar rats by renal mass ablation and vascular calcification was induced with a high calcium-phosphate diet and vitamin D supplementation (Ca/P/VitD). At week 3-6, hemodynamic parameters were determined and thoracic aorta was harvested for assessment of vascular calcification, macrophage infiltration, cytokines expression, VSMC differentiation, ROS generation, and related signaling pathway activation.
  
  
  RESULTS
  CKD rats treated with Ca/P/VitD developed medial calcification of thoracic aorta and increased pulse pressure and aortic pulse wave velocity. VSMC differentiation was confirmed by increased bone morphogenetic protein-2 and osteocalcin expression and reduced α-smooth muscle actin expression. The expression of interleukin-1β, interleukin-6, and tumor necrosis factor were also increased. The expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) were increased, whereas the expression of antioxidant enzymes (SOD1, SOD2, Gpx1, and Prdx1) was reduced in CKD + Ca/P/VitD rats. Oxidized peroxiredoxin, a sensor of ROS generation, was significantly increased and ROS-sensitive signaling pathways were activated in the aorta from CKD + Ca/P/VitD rats.
  
  
  CONCLUSIONS
  This study demonstrates a relationship between inflammation/ROS and arterial calcification in CKD and contributes to understanding of the complex pathways that mediate arterial calcification in CKD patients.
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada; Département de médecine , Faculté de Médecine, Université Laval, Québec, QC, Canada; mohsen.agharazii@crhdq.ulaval.ca.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Agharazii
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada;
authors.forename: Ronald
authors.initials: R
authors.lastname: St-Louis
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gautier-Bastien
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada;
authors.forename: Roth-Visal
authors.initials: RV
authors.lastname: Ung
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada;
authors.forename: Sophie
authors.initials: S
authors.lastname: Mokas
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada; Département de médecine , Faculté de Médecine, Université Laval, Québec, QC, Canada;
authors.forename: Richard
authors.initials: R
authors.lastname: Larivière
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, QC, Canada; Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Darren E
authors.initials: DE
authors.lastname: Richard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D005979:Glutathione Peroxidase; D053583:Interleukin-1beta; D015850:Interleukin-6; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C508600:IL6 protein, human; C000722069:Gpx1 protein, rat
keywords: NADPH oxidase; blood pressure; chronic kidney disease; hypertension; inflammatory cytokines; reactive oxygen species; vascular calcification.