Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve

Sanjay Rajagopalan, Manan Shah, Ann Luciano, Ronald Crystal, Elizabeth G. Nabel

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Background - Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (AdGVVEGF121.10) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF121.10. Methods and Results - Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of AdGVVEGF121.10, in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with AdGVVEGF121.10. In response to acetylcholine (150 μg/min and 300 μg/min), there was a 0.9-fold (0.33±0.03 to 0.32±0.03 L/min) and 1.2-fold (0.33±0.03 to 0.490±0.02 L/min) change in flow before AdGVVEGF121.10 treatment. After AdGVVEGF121.10 treatment, flow increased 2.4-fold (0.310±0.04 to 0.730±0.10 L/min) and 2.3-fold (0.31±0.04 to 0.7±0.08 L/min), respectively (P<0.05 before AdGVVEGF121.10 treatment versus after AdGVVEGF121.10 for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before AdGVVEGF121.10 (0.33±0.03 to 0.58±0.06 L/min) compared with a 2.4-fold increase (0.31±0.04 to 0.73±0.09 L/min) after AdGVVEGF121.10 (P=NS before AdGVVEGF121.10 versus after AdGVVEGF121.10). Lower-extremity flow reserve increased in all patients in response to at least 1 dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. Conclusions - Adenoviral gene transfer of VEGF121.10 appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.

Original languageEnglish
Pages (from-to)753-755
Number of pages3
JournalCirculation
Volume104
Issue number7
DOIs
Publication statusPublished - 14 Aug 2001
Externally publishedYes

Fingerprint

Adenoviridae
Lower Extremity
Genes
Peripheral Arterial Disease
Nitroglycerin
Vascular Endothelial Growth Factor A
Acetylcholine
AdGVVEGF121.10
Cholinergic Agonists
Thermodilution
Femoral Artery
Therapeutics
Walking
Endothelium
Skeletal Muscle
Extremities
Clinical Trials

Keywords

  • Angiogenesis
  • Endothelium
  • Gene therapy
  • Growth substances
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve. / Rajagopalan, Sanjay; Shah, Manan; Luciano, Ann; Crystal, Ronald; Nabel, Elizabeth G.

In: Circulation, Vol. 104, No. 7, 14.08.2001, p. 753-755.

Research output: Contribution to journalArticle

Rajagopalan, Sanjay ; Shah, Manan ; Luciano, Ann ; Crystal, Ronald ; Nabel, Elizabeth G. / Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve. In: Circulation. 2001 ; Vol. 104, No. 7. pp. 753-755.
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AU - Shah, Manan

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AU - Nabel, Elizabeth G.

PY - 2001/8/14

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N2 - Background - Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (AdGVVEGF121.10) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF121.10. Methods and Results - Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of AdGVVEGF121.10, in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with AdGVVEGF121.10. In response to acetylcholine (150 μg/min and 300 μg/min), there was a 0.9-fold (0.33±0.03 to 0.32±0.03 L/min) and 1.2-fold (0.33±0.03 to 0.490±0.02 L/min) change in flow before AdGVVEGF121.10 treatment. After AdGVVEGF121.10 treatment, flow increased 2.4-fold (0.310±0.04 to 0.730±0.10 L/min) and 2.3-fold (0.31±0.04 to 0.7±0.08 L/min), respectively (P<0.05 before AdGVVEGF121.10 treatment versus after AdGVVEGF121.10 for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before AdGVVEGF121.10 (0.33±0.03 to 0.58±0.06 L/min) compared with a 2.4-fold increase (0.31±0.04 to 0.73±0.09 L/min) after AdGVVEGF121.10 (P=NS before AdGVVEGF121.10 versus after AdGVVEGF121.10). Lower-extremity flow reserve increased in all patients in response to at least 1 dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. Conclusions - Adenoviral gene transfer of VEGF121.10 appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.

AB - Background - Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (AdGVVEGF121.10) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF121.10. Methods and Results - Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of AdGVVEGF121.10, in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with AdGVVEGF121.10. In response to acetylcholine (150 μg/min and 300 μg/min), there was a 0.9-fold (0.33±0.03 to 0.32±0.03 L/min) and 1.2-fold (0.33±0.03 to 0.490±0.02 L/min) change in flow before AdGVVEGF121.10 treatment. After AdGVVEGF121.10 treatment, flow increased 2.4-fold (0.310±0.04 to 0.730±0.10 L/min) and 2.3-fold (0.31±0.04 to 0.7±0.08 L/min), respectively (P<0.05 before AdGVVEGF121.10 treatment versus after AdGVVEGF121.10 for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before AdGVVEGF121.10 (0.33±0.03 to 0.58±0.06 L/min) compared with a 2.4-fold increase (0.31±0.04 to 0.73±0.09 L/min) after AdGVVEGF121.10 (P=NS before AdGVVEGF121.10 versus after AdGVVEGF121.10). Lower-extremity flow reserve increased in all patients in response to at least 1 dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. Conclusions - Adenoviral gene transfer of VEGF121.10 appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.

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