Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion

C. A. Mack, C. J. Magovern, K. T. Budenbender, S. R. Patel, E. A. Schwarz, P. Zanzonico, B. Ferris, T. Sanborn, O. W. Isom, Ronald Crystal, T. K. Rosengart

Research output: Contribution to journalArticle

124 Citations (Scopus)

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 lilac artery immediately followed by administration of 4 x 109-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 μm 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.

Original languageEnglish
Pages (from-to)699-709
Number of pages11
JournalJournal of Vascular Surgery
Volume27
Issue number4
DOIs
Publication statusPublished - 1 Jan 1998
Externally publishedYes

Fingerprint

Adenoviridae
Vascular Endothelial Growth Factor A
Blood Vessels
Hindlimb
Ligation
Ischemia
Thigh
Genes
Control Groups
Complementary DNA
Femoral Artery
Adipose Tissue
Technetium Tc 99m Sestamibi
Muscles
Arterial Occlusive Diseases
Angiogenesis Inducing Agents
Transgenes
Microspheres
Sodium Chloride
Radioisotopes

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. / Mack, C. A.; Magovern, C. J.; Budenbender, K. T.; Patel, S. R.; Schwarz, E. A.; Zanzonico, P.; Ferris, B.; Sanborn, T.; Isom, O. W.; Crystal, Ronald; Rosengart, T. K.

In: Journal of Vascular Surgery, Vol. 27, No. 4, 01.01.1998, p. 699-709.

Research output: Contribution to journalArticle

Mack, CA, Magovern, CJ, Budenbender, KT, Patel, SR, Schwarz, EA, Zanzonico, P, Ferris, B, Sanborn, T, Isom, OW, Crystal, R & Rosengart, TK 1998, '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, pp. 699-709. https://doi.org/10.1016/S0741-5214(98)70236-8
Mack, C. A. ; Magovern, C. J. ; Budenbender, K. T. ; Patel, S. R. ; Schwarz, E. A. ; Zanzonico, P. ; Ferris, B. ; Sanborn, T. ; Isom, O. W. ; Crystal, Ronald ; Rosengart, T. K. / Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion. In: Journal of Vascular Surgery. 1998 ; Vol. 27, No. 4. pp. 699-709.
@article{4d51c37704194a28a3a362538016aed0,
title = "Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion",
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 lilac artery immediately followed by administration of 4 x 109-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 μm 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.",
author = "Mack, {C. A.} and Magovern, {C. J.} and Budenbender, {K. T.} and Patel, {S. R.} and Schwarz, {E. A.} and P. Zanzonico and B. Ferris and T. Sanborn and Isom, {O. W.} and Ronald Crystal and Rosengart, {T. K.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1016/S0741-5214(98)70236-8",
language = "English",
volume = "27",
pages = "699--709",
journal = "Journal of Vascular Surgery",
issn = "0741-5214",
publisher = "Mosby Inc.",
number = "4",

}

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, O. W.

AU - Crystal, Ronald

AU - Rosengart, T. K.

PY - 1998/1/1

Y1 - 1998/1/1

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 lilac artery immediately followed by administration of 4 x 109-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 μm 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.

AB - 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 lilac artery immediately followed by administration of 4 x 109-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 μm 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.

UR - http://www.scopus.com/inward/record.url?scp=0031939157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031939157&partnerID=8YFLogxK

U2 - 10.1016/S0741-5214(98)70236-8

DO - 10.1016/S0741-5214(98)70236-8

M3 - Article

C2 - 9576084

AN - SCOPUS:0031939157

VL - 27

SP - 699

EP - 709

JO - Journal of Vascular Surgery

JF - Journal of Vascular Surgery

SN - 0741-5214

IS - 4

ER -