title: αKlotho and vascular calcification: an evolving paradigm.
abstract: OBJECTIVE
  Cardiovascular disease remains the single most serious contributor to mortality in chronic kidney disease (CKD). Although conventional risk factors are prevalent in CKD, both cardiomyopathy and vasculopathy can be caused by pathophysiologic mechanisms specific to the uremic state. CKD is a state of systemic αKlotho deficiency. Although the molecular mechanism of action of αKlotho is not well understood, the downstream targets and biologic functions of αKlotho are astonishingly pleiotropic. An emerging body of literature links αKlotho to uremic vasculopathy.
  
  
  RESULTS
  The expression of αKlotho in the vasculature is controversial because of conflicting data. Regardless of whether αKlotho acts as a circulating or resident protein, there are good data associating changes in αKlotho levels with vascular pathology including vascular calcification and in-vitro data of the direct action of αKlotho on both the endothelium and vascular smooth muscle cells in terms of cytoprotection and prevention of mineralization.
  
  
  CONCLUSIONS
  It is critical to understand the pathogenic role of αKlotho on the integral endothelium-vascular smooth muscle network rather than each cell type in isolation in uremic vasculopathy, as αKlotho can serve as a potential prognostic biomarker and a biological therapeutic agent.
authors.affiliation: aDepartment of Internal Medicine bThe Charles and Jane Pak Center of Mineral Metabolism and Clinical Research cDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA dCenter for Molecular Medicine, Jichi Medical University Tochigi, Japan eDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Ming Chang
authors.initials: MC
authors.lastname: Hu
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-o
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
mesh_terms: D000818:Animals; D004727:Endothelium / Q000503:physiopathology*; D005966:Glucuronidase / Q000097:blood* / Q000172:deficiency; D006801:Humans; D000090265:Klotho Proteins; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D014511:Uremia / Q000097:blood; D061205:Vascular Calcification / Q000097:blood*; D059289:Vascular Stiffness
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins