title: Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling.
abstract: BACKGROUND
  In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF).
  
  
  METHODS
  Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms.
  
  
  RESULTS
  Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1.
  
  
  CONCLUSIONS
  Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.
authors.affiliation: Department of Anatomy, Histology and Forensic Medicine, University of Firenze, Firenze, Italy. stefania.pacini@unifi.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Pacini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Morucci
authors.forename: Tiziana
authors.initials: T
authors.lastname: Punzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Gulisano
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggiero
authors.forename: Marcello
authors.initials: M
authors.lastname: Amato
authors.forename: Stefano
authors.initials: S
authors.lastname: Aterini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D006152:Cyclic GMP / Q000378:metabolism; D004872:Ergocalciferols / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016215:Macrophage-Activating Factors / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010641:Phenotype; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014809:Vitamin D-Binding Protein / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D004872:Ergocalciferols; D016215:Macrophage-Activating Factors; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; C101908:vitamin D-binding protein-macrophage activating factor; C084656:paricalcitol; D006152:Cyclic GMP