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Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion.
J Vasc Surg. 1998 Apr; 27(4):699-709.JV

Abstract

PURPOSE

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion.

METHODS

Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group.

RESULTS

Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04).

CONCLUSIONS

An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.

Authors+Show Affiliations

Department of Cardiothoracic Surgery, The New York Hospital-Cornell Medical Center, NY 10021, USA.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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9576084

Citation

Mack, C A., et al. "Salvage Angiogenesis Induced By Adenovirus-mediated Gene Transfer of Vascular Endothelial Growth Factor Protects Against Ischemic Vascular Occlusion." Journal of Vascular Surgery, vol. 27, no. 4, 1998, pp. 699-709.
Mack CA, Magovern CJ, Budenbender KT, et al. Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. J Vasc Surg. 1998;27(4):699-709.
Mack, C. A., Magovern, C. J., Budenbender, K. T., Patel, S. R., Schwarz, E. A., Zanzonico, P., Ferris, B., Sanborn, T., Isom, P., Ferris, B., Sanborn, T., Isom, O. W., Crystal, R. G., & Rosengart, T. K. (1998). Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. Journal of Vascular Surgery, 27(4), 699-709.
Mack CA, et al. Salvage Angiogenesis Induced By Adenovirus-mediated Gene Transfer of Vascular Endothelial Growth Factor Protects Against Ischemic Vascular Occlusion. J Vasc Surg. 1998;27(4):699-709. PubMed PMID: 9576084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. AU - Mack,C A, AU - Magovern,C J, AU - Budenbender,K T, AU - Patel,S R, AU - Schwarz,E A, AU - Zanzonico,P, AU - Ferris,B, AU - Sanborn,T, AU - Isom,P, AU - Ferris,B, AU - Sanborn,T, AU - Isom,O W, AU - Crystal,R G, AU - Rosengart,T K, PY - 1998/5/12/pubmed PY - 1998/5/12/medline PY - 1998/5/12/entrez SP - 699 EP - 709 JF - Journal of vascular surgery JO - J Vasc Surg VL - 27 IS - 4 N2 - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease. SN - 0741-5214 UR - https://www.unboundmedicine.com/medline/citation/9576084/Salvage_angiogenesis_induced_by_adenovirus_mediated_gene_transfer_of_vascular_endothelial_growth_factor_protects_against_ischemic_vascular_occlusion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0741521498001219 DB - PRIME DP - Unbound Medicine ER -