Original investigation

Cardiovascular Diabetology

, 2:18

Open Access This content is freely available online to anyone, anywhere at any time.

Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model

  • Ariel RoguinAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of TechnologyDepartment of Cardiology, Rambam Medical CenterDivision of Cardiology, The Johns Hopkins Hospital Email author 
  • , Samy NiteckiAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of TechnologyDepartment of Vascular Surgery, Rambam Medical Center Email author 
  • , Irit RubinsteinAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 
  • , Eviatar NevoAffiliated withInstitute of Evolution, University of Haifa Email author 
  • , Aaron AviviAffiliated withInstitute of Evolution, University of Haifa Email author 
  • , Nina S LevyAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 
  • , Zaid A AbassiAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 
  • , Edmond SaboAffiliated withDepartment of Pathology, Lady Davis Carmel Medical Center Email author 
  • , Orit LacheAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 
    • , Meira FrankAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 
    • , Aaron HoffmanAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of TechnologyDepartment of Vascular Surgery, Rambam Medical Center Email author 
    • , Andrew P LevyAffiliated withBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology Email author 

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.

arteries blood flow collateral circulation diabetes