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Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene.
Circulation. 1997 Nov 04; 96(9 Suppl):II-382-8.Circ

Abstract

BACKGROUND

Ischemic skeletal muscle has been shown to be advantageous for taking up and expressing genes transferred in the form of naked plasmid DNA. Therefore, acutely ischemic skeletal muscle may represent a potential target for IM gene therapy with naked DNA. Accordingly, we investigated the impact of IM injection of plasmid DNA encoding the secreted angiogenic growth factor, vascular endothelial growth factor (VEGF), on collateral vessel development in an animal model of acute hindlimb ischemia.

METHODS AND RESULTS

After ligation of distal external iliac artery in New Zealand White rabbits, we directly injected 500 microg of phVEGF165 into the ischemic thigh muscles. At 30 days posttransfection, VEGF-transfected animals had more angiographically recognizable collateral vessels (angiographic score=0.72+/-0.06 versus 0.48+/-0.10; P<.01) as well as histologically assessed capillaries (248+/-37 versus 180+/-32/mm2, P<.01) compared to controls. Hemodynamic deficit was less severe in VEGF-transfected animals by calf systolic blood pressure ratio (0.80+/-0.09 versus 0.56+/-0.10, P<.01) and by flow to the ischemic limb measured with Doppler guidewire (resting flow=22+/-5 versus 14+/-4; P<.01; hyperemic flow=59+/-17 versus 39+/-12 mL/min; P<.05). Human VEGF mRNA was expressed in the transfected ischemic muscles as long as 14 days after gene transfer. Based on reporter plasmid expression, transfection efficiency was sixfold higher in ischemic muscles than in nonischemic control muscles.

CONCLUSIONS

These results suggest the feasibility of employing direct IM transfer of naked VEGF plasmid DNA to optimize treatment of acute limb ischemia.

Authors+Show Affiliations

Department of Medicine, St Elizabeth's Medical Center of Boston, Tufts University School of Medicine, Mass 02135, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9386128

Citation

Tsurumi, Y, et al. "Treatment of Acute Limb Ischemia By Intramuscular Injection of Vascular Endothelial Growth Factor Gene." Circulation, vol. 96, no. 9 Suppl, 1997, pp. II-382-8.
Tsurumi Y, Kearney M, Chen D, et al. Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation. 1997;96(9 Suppl):II-382-8.
Tsurumi, Y., Kearney, M., Chen, D., Silver, M., Takeshita, S., Yang, J., Symes, J. F., & Isner, J. M. (1997). Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation, 96(9 Suppl), II-382-8.
Tsurumi Y, et al. Treatment of Acute Limb Ischemia By Intramuscular Injection of Vascular Endothelial Growth Factor Gene. Circulation. 1997 Nov 4;96(9 Suppl):II-382-8. PubMed PMID: 9386128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. AU - Tsurumi,Y, AU - Kearney,M, AU - Chen,D, AU - Silver,M, AU - Takeshita,S, AU - Yang,J, AU - Symes,J F, AU - Isner,J M, PY - 1997/12/31/pubmed PY - 1997/12/31/medline PY - 1997/12/31/entrez SP - II-382-8 JF - Circulation JO - Circulation VL - 96 IS - 9 Suppl N2 - BACKGROUND: Ischemic skeletal muscle has been shown to be advantageous for taking up and expressing genes transferred in the form of naked plasmid DNA. Therefore, acutely ischemic skeletal muscle may represent a potential target for IM gene therapy with naked DNA. Accordingly, we investigated the impact of IM injection of plasmid DNA encoding the secreted angiogenic growth factor, vascular endothelial growth factor (VEGF), on collateral vessel development in an animal model of acute hindlimb ischemia. METHODS AND RESULTS: After ligation of distal external iliac artery in New Zealand White rabbits, we directly injected 500 microg of phVEGF165 into the ischemic thigh muscles. At 30 days posttransfection, VEGF-transfected animals had more angiographically recognizable collateral vessels (angiographic score=0.72+/-0.06 versus 0.48+/-0.10; P<.01) as well as histologically assessed capillaries (248+/-37 versus 180+/-32/mm2, P<.01) compared to controls. Hemodynamic deficit was less severe in VEGF-transfected animals by calf systolic blood pressure ratio (0.80+/-0.09 versus 0.56+/-0.10, P<.01) and by flow to the ischemic limb measured with Doppler guidewire (resting flow=22+/-5 versus 14+/-4; P<.01; hyperemic flow=59+/-17 versus 39+/-12 mL/min; P<.05). Human VEGF mRNA was expressed in the transfected ischemic muscles as long as 14 days after gene transfer. Based on reporter plasmid expression, transfection efficiency was sixfold higher in ischemic muscles than in nonischemic control muscles. CONCLUSIONS: These results suggest the feasibility of employing direct IM transfer of naked VEGF plasmid DNA to optimize treatment of acute limb ischemia. SN - 0009-7322 UR - https://www.unboundmedicine.com/medline/citation/9386128/Treatment_of_acute_limb_ischemia_by_intramuscular_injection_of_vascular_endothelial_growth_factor_gene_ L2 - https://medlineplus.gov/genesandgenetherapy.html DB - PRIME DP - Unbound Medicine ER -