title: Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature.
abstract: Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and increases mortality in those patients. Impaired calcium and phosphate homeostasis, increased oxidative stress, and loss of calcification inhibitors have been linked to vascular calcification in CKD. Additionally, impaired bone may perturb serum calcium/phosphate and their key regulator, parathyroid hormone, thus contributing to increased vascular calcification in CKD. Therapeutic approaches for CKD, such as phosphate binders and bisphosphonates, have been shown to ameliorate bone loss as well as vascular calcification. The precise mechanisms responsible for vascular calcification in CKD and the contribution of bone metabolism to vascular calcification have not been elucidated. This review discusses the role of systemic uremic factors and impaired bone metabolism in the pathogenesis of vascular calcification in CKD. The regulation of the key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of CKD are emphasized.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 614 Shelby Biomedical Research Bldg., 1825 University Blvd., Birmingham, AL, 35294, USA, chbyon@uab.edu.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Byon
authors.forename: Yabing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006801:Humans; D010024:Osteoporosis / Q000150:complications*; D053245:RANK Ligand / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000473:pathology*; D061205:Vascular Calcification / Q000473:pathology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053245:RANK Ligand; C493709:RUNX2 protein, human; C505688:TNFSF11 protein, human