Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model
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.
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.
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.
Angiogenic therapy with VEGF in the setting of diabetes does not appear to have the beneficial effects seen in the absence of diabetes.
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- Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model
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- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- December 2003
- Online ISSN
- BioMed Central
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- Author Affiliations
- 1. Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel
- 2. Department of Cardiology, Rambam Medical Center, Bat Galim, Haifa, 31096, Israel
- 6. Division of Cardiology, The Johns Hopkins Hospital, Traylor 903, 720 Rutland Ave., Baltimore, MD, 21205, USA
- 3. Department of Vascular Surgery, Rambam Medical Center, Bat Galim, Haifa, 31096, Israel
- 5. Institute of Evolution, University of Haifa, 31095, Haifa, Israel
- 4. Department of Pathology, Lady Davis Carmel Medical Center, 7 Michal St, Haifa, Israel, 34362