title: Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model.
abstract: BACKGROUND
  Angiogenic therapy with vascular endothelial growth factor (VEGF) has been proposed as a treatment paradigm for patients suffering from an insufficiency of collateral vessels. Diabetes is associated with increase in the production of VEGF and therefore additional VEGF may not be beneficial. Accordingly, we sought to determine the efficacy of VEGF therapy to augment collateral formation and tissue perfusion in a diabetic mouse ischemic hindlimb model.
  
  
  METHODS
  Diabetic and non-diabetic mice were studied in parallel for the efficacy of VEGF administration. Diabetes was induced with streptozotocin. Hindlimb ischemia was produced by severing the left iliac artery. An outlet tube from an osmotic infusion pump with placebo/500 micrograms of plasmid-DNA encoding VEGF was fenestrated and tunneled into the left quadriceps muscle.
  
  
  RESULTS
  VEGF induced more rapid and complete restoration of blood flow in normal mice. However, in the setting of diabetes there was no difference between VEGF vs. placebo in the rate or adequacy of flow restoration. There was a significant increase in smooth muscle actin and Factor-VIII antigen densities in diabetic animals and in animals which received VEGF.
  
  
  CONCLUSIONS
  Angiogenic therapy with VEGF in the setting of diabetes does not appear to have the beneficial effects seen in the absence of diabetes.
authors.affiliation: Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel. aroguin1@jhmi.edu
authors.forename: Ariel
authors.initials: A
authors.lastname: Roguin
authors.forename: Samy
authors.initials: S
authors.lastname: Nitecki
authors.forename: Irit
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Eviatar
authors.initials: E
authors.lastname: Nevo
authors.forename: Aaron
authors.initials: A
authors.lastname: Avivi
authors.forename: Nina S
authors.initials: NS
authors.lastname: Levy
authors.forename: Zaid A
authors.initials: ZA
authors.lastname: Abassi
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Orit
authors.initials: O
authors.lastname: Lache
authors.forename: Meira
authors.initials: M
authors.lastname: Frank
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoffman
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy