title: The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation.
abstract: OBJECTIVE
  To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia.
  
  
  METHODS
  Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 10(6) plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses.
  
  
  RESULTS
  By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P < .0001; day 28, P < .05; day 42, P = .59), and decrease in hypoxic stress (day 21, P < .001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels.
  
  
  CONCLUSIONS
  A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.
authors.affiliation: Amity Institute of Public Health, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India; Vascular and Interventional Radiology Translational Laboratory Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Janardhanan
authors.affiliation: Amity Institute of Public Health, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India; Vascular and Interventional Radiology Translational Laboratory Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors.forename: Binxia
authors.initials: B
authors.lastname: Yang
authors.affiliation: Amity Institute of Public Health, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India; Vascular and Interventional Radiology Translational Laboratory Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Kilari
authors.affiliation: Department of Radiology, and Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Leof
authors.affiliation: Department of Radiology, and Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: Amity Institute of Public Health, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India; Vascular and Interventional Radiology Translational Laboratory Mayo Clinic, 200 First Street SW, Rochester, MN 55905; Department of Radiology, and Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Electronic address: misra.sanjay@mayo.edu.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
mesh_terms: D000199:Actins / Q000378:metabolism; D063194:Adventitia / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D002339:Carotid Arteries / Q000601:surgery; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007601:Jugular Veins / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D058426:Neointima; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000628:therapy*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: D000199:Actins; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C467480:vascular endothelial growth factor A, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse