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Local perivascular application of low amounts of a plasmid encoding for vascular endothelial growth factor (VEGF165) is efficient for therapeutic angiogenesis in pigs.
Acta Physiol Scand. 2002 Oct; 176(2):151-9.AP

Abstract

Clinical trials have demonstrated therapeutic benefit in inducing angiogenesis in chronic occlusive arterial disease. The route of application mostly used was the intramuscular injection of high dosages of plasmid. Therefore, a local perivascular application of low amounts of vascular endothelial growth factor (VEGF) plasmid was used in an interventional occlusion model, and the effect of VEGF on coronary and peripheral occlusions compared in the same animal model. Coronary and peripheral arteries were chronically occluded in Pietrain pigs using a non-surgical, interventional approach. Adventitial delivery of the DNA for VEGF was performed with a needle injection catheter. The DNA was applied as lipoplexes using the novel cationic liposomes DOCSPER. Optimized transfer conditions were used. Angiography, polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were undertaken within a follow-up period of 6 months. Expression of the transfected VEGF gene was observed at 1 and 3 weeks following application. The DNA was detected up to 5 months following application. Around occluded coronary arteries, there was formation of new collaterals and arterial prolongation, whereas surrounding occluded peripheral arteries there was no collateralization but development of new arterial branches was seen. Results demonstrate that the response to VEGF is also sufficient, when minimal amounts of plasmid encoding for VEGF are applied locally into the perivasculature allowing for more safety of this therapy. Comparison of treatment of chronic coronary and peripheral arterial disease revealed differences in angiogenesis following VEGF application during a total follow-up period of almost 6 months which may be related to their different developmental origins. This may have important implications for developing future therapeutic strategies using VEGF in different vessels.

Authors+Show Affiliations

Medical Clinic I, Klinikum Grosshadern, Ludwig Maximilian University of Munich, Germany. nikol@uni-muenster.deNo 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, Non-U.S. Gov't

Language

eng

PubMed ID

12354175

Citation

Nikol, S, et al. "Local Perivascular Application of Low Amounts of a Plasmid Encoding for Vascular Endothelial Growth Factor (VEGF165) Is Efficient for Therapeutic Angiogenesis in Pigs." Acta Physiologica Scandinavica, vol. 176, no. 2, 2002, pp. 151-9.
Nikol S, Engelmann MG, Pelisek J, et al. Local perivascular application of low amounts of a plasmid encoding for vascular endothelial growth factor (VEGF165) is efficient for therapeutic angiogenesis in pigs. Acta Physiol Scand. 2002;176(2):151-9.
Nikol, S., Engelmann, M. G., Pelisek, J., Fuchs, A., Golda, A., Shimizu, M., Mekkaoui, C., & Rolland, P. H. (2002). Local perivascular application of low amounts of a plasmid encoding for vascular endothelial growth factor (VEGF165) is efficient for therapeutic angiogenesis in pigs. Acta Physiologica Scandinavica, 176(2), 151-9.
Nikol S, et al. Local Perivascular Application of Low Amounts of a Plasmid Encoding for Vascular Endothelial Growth Factor (VEGF165) Is Efficient for Therapeutic Angiogenesis in Pigs. Acta Physiol Scand. 2002;176(2):151-9. PubMed PMID: 12354175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Local perivascular application of low amounts of a plasmid encoding for vascular endothelial growth factor (VEGF165) is efficient for therapeutic angiogenesis in pigs. AU - Nikol,S, AU - Engelmann,M G, AU - Pelisek,J, AU - Fuchs,A, AU - Golda,A, AU - Shimizu,M, AU - Mekkaoui,C, AU - Rolland,P H, PY - 2002/10/2/pubmed PY - 2003/2/25/medline PY - 2002/10/2/entrez SP - 151 EP - 9 JF - Acta physiologica Scandinavica JO - Acta Physiol Scand VL - 176 IS - 2 N2 - Clinical trials have demonstrated therapeutic benefit in inducing angiogenesis in chronic occlusive arterial disease. The route of application mostly used was the intramuscular injection of high dosages of plasmid. Therefore, a local perivascular application of low amounts of vascular endothelial growth factor (VEGF) plasmid was used in an interventional occlusion model, and the effect of VEGF on coronary and peripheral occlusions compared in the same animal model. Coronary and peripheral arteries were chronically occluded in Pietrain pigs using a non-surgical, interventional approach. Adventitial delivery of the DNA for VEGF was performed with a needle injection catheter. The DNA was applied as lipoplexes using the novel cationic liposomes DOCSPER. Optimized transfer conditions were used. Angiography, polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were undertaken within a follow-up period of 6 months. Expression of the transfected VEGF gene was observed at 1 and 3 weeks following application. The DNA was detected up to 5 months following application. Around occluded coronary arteries, there was formation of new collaterals and arterial prolongation, whereas surrounding occluded peripheral arteries there was no collateralization but development of new arterial branches was seen. Results demonstrate that the response to VEGF is also sufficient, when minimal amounts of plasmid encoding for VEGF are applied locally into the perivasculature allowing for more safety of this therapy. Comparison of treatment of chronic coronary and peripheral arterial disease revealed differences in angiogenesis following VEGF application during a total follow-up period of almost 6 months which may be related to their different developmental origins. This may have important implications for developing future therapeutic strategies using VEGF in different vessels. SN - 0001-6772 UR - https://www.unboundmedicine.com/medline/citation/12354175/Local_perivascular_application_of_low_amounts_of_a_plasmid_encoding_for_vascular_endothelial_growth_factor__VEGF165__is_efficient_for_therapeutic_angiogenesis_in_pigs_ L2 - https://doi.org/10.1046/j.1365-201X.2002.01018.x DB - PRIME DP - Unbound Medicine ER -