title: An efficacy of intensive vitamin D delivery to neointimal hyperplasia in recurrent vascular access stenosis.
abstract: OBJECTIVE
  Neointimal hyperplasia (NH) causes vascular access (VA) stenosis, which results in serious under-dialytic morbidity in hemodialysis patients. We sought to assess whether a vitamin D intervention to NH lesions leads to better VA patency and examined clinical and in vitro studies.
  
  
  METHODS
  A pilot clinical study of six hemodialysis patients was conducted to elucidate whether 0.5 μg calcitriol injection to stenotic lesion after balloon angioplasty (PTA) maintains better vessel patency until the next follow-up angiography. Localized vitamin D exposure was utilized by delivering and fixing calcitriol intensively at the stenotic lesion through a side-hole catheter with balloon clamping. We also performed vascular smooth muscle cell (VSMC) culture to detect both apoptosis (cell death detection assay) and cell viability (5-Bromo-2'-deoxy-uridine incorporation), and explored the efficacy of vitamin D to inhibit VSMC proliferation. Additionally, immunohistochemistry (IHC) was conducted to examine vitamin D receptor (VDR) expression at NH lesion, obtained from VA surgery.
  
  
  RESULTS
  Percent patency, the proportion between stenotic and non-stenotic vessel diameters, increased significantly (p = 0.03) after directly catheter-delivered 0.5 μg calcitriol administration. In vitro VSMC studies, 0.1 nM calcitriol significantly (p<0.05) enhanced apoptosis and cell-cycle inhibition for two different calcitriol exposure times (15 minutes and 24 hours). IHC staining revealed that VDR-positive hyperplastic cells were observed at NH lesion.
  
  
  CONCLUSIONS
  Intensive vitamin D exposure at NH lesion has an ability to inhibit further VSMC proliferation, and presumably leads to greater patency rate for recurrent VA stenosis. Further studies are needed to clarify whether its unique property is exhibited through VDR-mediated mechanism.
authors.affiliation: Division of Diabetes and Endocrinology, Nagoya Daini Red Cross Hospital, Nagoya - Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita - Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo - Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.affiliation: Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara - Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000800:Angioplasty, Balloon; D017209:Apoptosis / Q000187:drug effects; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D002117:Calcitriol / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006083:Graft Occlusion, Vascular / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima; D010865:Pilot Projects; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D012008:Recurrence; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002117:Calcitriol