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Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ.
J Gene Med. 2002 Jul-Aug; 4(4):371-80.JG

Abstract

BACKGROUND

Recent studies have suggested the therapeutic potential of vascular endothelial growth factor (VEGF) gene therapy in ischemic skeletal muscle. However, only limited information is available about the effects of VEGF gene therapy in different regions of ischemic limbs, effects of control adenoviruses, and biodistribution of the transgenes after intramuscular (i.m.) administration. Here we studied angiogenesis and side effects of adenovirus-mediated VEGF and beta-galactosidase (LacZ) gene transfers in ischemic rabbit hindlimbs.

METHODS AND RESULTS

Ten days after induction of ischemia, rabbits were treated with i.m. injections of saline, LacZ adenovirus (AdLacZ; 2x10(10) pfu) or adenovirus encoding mouse VEGF(164) (AdVEGF; 2x10(10) pfu). In rabbits treated with AdVEGF an increase in serum VEGF(164) levels was detected by ELISA three and seven days after the gene transfer. 30 days after the gene transfer a positive effect on capillary density was observed in the thigh region both in rabbits treated with AdVEGF and AdLacZ compared with animals that received saline. On the other hand, AdVEGF and AdLacZ gene transfers had no effect on the capillary density in the calf region on day 30. A positive correlation between the capillary density and the number of collateral arteries was observed in the thigh. Hindlimb and testis edema and excess non-physiological growth of capillaries were detected as adverse effects of the AdVEGF gene therapy. Biodistribution analysis showed that the transgene was present not only in the target muscle, but also in ectopic tissues seven days after i.m. gene transfer.

CONCLUSIONS

The results suggest that a high dose of adenoviral vector encoding either AdVEGF or AdLacZ induces angiogenesis in the rabbit hindlimb ischemia model; i.m. injection of adenovirus leads to the transfection of ectopic organs; and AdVEGF gene transfer induces edema in ischemic skeletal muscle.

Authors+Show Affiliations

A.I. Virtanen Institute, Kuopio University, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

12124979

Citation

Vajanto, Ismo, et al. "Evaluation of Angiogenesis and Side Effects in Ischemic Rabbit Hindlimbs After Intramuscular Injection of Adenoviral Vectors Encoding VEGF and LacZ." The Journal of Gene Medicine, vol. 4, no. 4, 2002, pp. 371-80.
Vajanto I, Rissanen TT, Rutanen J, et al. Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. J Gene Med. 2002;4(4):371-80.
Vajanto, I., Rissanen, T. T., Rutanen, J., Hiltunen, M. O., Tuomisto, T. T., Arve, K., Närvänen, O., Manninen, H., Räsänen, H., Hippeläinen, M., Alhava, E., & Ylä-Herttuala, S. (2002). Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. The Journal of Gene Medicine, 4(4), 371-80.
Vajanto I, et al. Evaluation of Angiogenesis and Side Effects in Ischemic Rabbit Hindlimbs After Intramuscular Injection of Adenoviral Vectors Encoding VEGF and LacZ. J Gene Med. 2002 Jul-Aug;4(4):371-80. PubMed PMID: 12124979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. AU - Vajanto,Ismo, AU - Rissanen,Tuomas T, AU - Rutanen,Juha, AU - Hiltunen,Mikko O, AU - Tuomisto,Tiina T, AU - Arve,Katja, AU - Närvänen,Outi, AU - Manninen,Hannu, AU - Räsänen,Heikki, AU - Hippeläinen,Mikko, AU - Alhava,Esko, AU - Ylä-Herttuala,Seppo, PY - 2002/7/19/pubmed PY - 2003/1/17/medline PY - 2002/7/19/entrez SP - 371 EP - 80 JF - The journal of gene medicine JO - J Gene Med VL - 4 IS - 4 N2 - BACKGROUND: Recent studies have suggested the therapeutic potential of vascular endothelial growth factor (VEGF) gene therapy in ischemic skeletal muscle. However, only limited information is available about the effects of VEGF gene therapy in different regions of ischemic limbs, effects of control adenoviruses, and biodistribution of the transgenes after intramuscular (i.m.) administration. Here we studied angiogenesis and side effects of adenovirus-mediated VEGF and beta-galactosidase (LacZ) gene transfers in ischemic rabbit hindlimbs. METHODS AND RESULTS: Ten days after induction of ischemia, rabbits were treated with i.m. injections of saline, LacZ adenovirus (AdLacZ; 2x10(10) pfu) or adenovirus encoding mouse VEGF(164) (AdVEGF; 2x10(10) pfu). In rabbits treated with AdVEGF an increase in serum VEGF(164) levels was detected by ELISA three and seven days after the gene transfer. 30 days after the gene transfer a positive effect on capillary density was observed in the thigh region both in rabbits treated with AdVEGF and AdLacZ compared with animals that received saline. On the other hand, AdVEGF and AdLacZ gene transfers had no effect on the capillary density in the calf region on day 30. A positive correlation between the capillary density and the number of collateral arteries was observed in the thigh. Hindlimb and testis edema and excess non-physiological growth of capillaries were detected as adverse effects of the AdVEGF gene therapy. Biodistribution analysis showed that the transgene was present not only in the target muscle, but also in ectopic tissues seven days after i.m. gene transfer. CONCLUSIONS: The results suggest that a high dose of adenoviral vector encoding either AdVEGF or AdLacZ induces angiogenesis in the rabbit hindlimb ischemia model; i.m. injection of adenovirus leads to the transfection of ectopic organs; and AdVEGF gene transfer induces edema in ischemic skeletal muscle. SN - 1099-498X UR - https://www.unboundmedicine.com/medline/citation/12124979/Evaluation_of_angiogenesis_and_side_effects_in_ischemic_rabbit_hindlimbs_after_intramuscular_injection_of_adenoviral_vectors_encoding_VEGF_and_LacZ_ L2 - https://doi.org/10.1002/jgm.287 DB - PRIME DP - Unbound Medicine ER -