Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia

Kou-Gi Shyu, Hang Chang, Jeffrey M. Isner

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation of the external iliac artery and the excision of the common and superficial femoral artery in one female WHHL rabbit, 250 μg of phVEGF165 (n = 8), 500 μg of pAng1* (n = 8), or 250 μg of phVEGF165 plus 500 μg of pAng1* (n = 8) was injected intramuscularly into the ischemic hindlimb muscles. Gross appearance of ischemic limb, collateral vessel formation and limb perfusion were assessed 30 days after treatment. The incidence of ischemic limb necrosis was higher in the animals treated by phVEGF165 or by pAng1* than in those treated by phVEGF165 plus pAng1* (100%, 75% and 14.3%, respectively; P = 0.002). Animals in the combination therapy group had a significantly higher calf blood pressure ratio at day 30 (VEGF plus Ang1* = 0.84 ± 0.06; VEGF = 0.54 ± 0.01; Ang1* = 0.59 ± 0.05; P <0.01). A combination therapy of VEGF plus Ang*1 had a significantly higher (P <0.01) angiographic score than either therapy alone. Capillary density (P <0.05) and capillary/muscle fiber ratio (P <0.01) of the combination therapy group were also significantly higher than that of either therapy alone. In conclusion, Ang1 can potentiate the angiogenic response to VEGF in the hyperlipidemic rabbit model of acute hindlimb ischemia. Intramuscular administration of cytokines on revascularization of the ischemic hindlimb model of hyperlipidemic rabbit is feasible.

Original languageEnglish
Pages (from-to)563-579
Number of pages17
JournalLife Sciences
Volume73
Issue number5
DOIs
Publication statusPublished - Jun 20 2003

Fingerprint

Angiopoietin-1
Hindlimb
Vascular Endothelial Growth Factor A
Ischemia
Rabbits
Extremities
Group Psychotherapy
Muscle
Animals
Muscles
Iliac Artery
Blood pressure
Femoral Artery
Ligation
Blood Vessels
Necrosis
Therapeutics
Perfusion
Cytokines
Hypertension

Keywords

  • Angiopoietin-1
  • Collateral circulation
  • Growth substances
  • Hypercholesterolemia
  • Peripheral vascular disease
  • VEGF

ASJC Scopus subject areas

  • Pharmacology

Cite this

Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia. / Shyu, Kou-Gi; Chang, Hang; Isner, Jeffrey M.

In: Life Sciences, Vol. 73, No. 5, 20.06.2003, p. 563-579.

Research output: Contribution to journalArticle

@article{782ca693f5404e399f506170fcc9c1f9,
title = "Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia",
abstract = "Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation of the external iliac artery and the excision of the common and superficial femoral artery in one female WHHL rabbit, 250 μg of phVEGF165 (n = 8), 500 μg of pAng1* (n = 8), or 250 μg of phVEGF165 plus 500 μg of pAng1* (n = 8) was injected intramuscularly into the ischemic hindlimb muscles. Gross appearance of ischemic limb, collateral vessel formation and limb perfusion were assessed 30 days after treatment. The incidence of ischemic limb necrosis was higher in the animals treated by phVEGF165 or by pAng1* than in those treated by phVEGF165 plus pAng1* (100{\%}, 75{\%} and 14.3{\%}, respectively; P = 0.002). Animals in the combination therapy group had a significantly higher calf blood pressure ratio at day 30 (VEGF plus Ang1* = 0.84 ± 0.06; VEGF = 0.54 ± 0.01; Ang1* = 0.59 ± 0.05; P <0.01). A combination therapy of VEGF plus Ang*1 had a significantly higher (P <0.01) angiographic score than either therapy alone. Capillary density (P <0.05) and capillary/muscle fiber ratio (P <0.01) of the combination therapy group were also significantly higher than that of either therapy alone. In conclusion, Ang1 can potentiate the angiogenic response to VEGF in the hyperlipidemic rabbit model of acute hindlimb ischemia. Intramuscular administration of cytokines on revascularization of the ischemic hindlimb model of hyperlipidemic rabbit is feasible.",
keywords = "Angiopoietin-1, Collateral circulation, Growth substances, Hypercholesterolemia, Peripheral vascular disease, VEGF",
author = "Kou-Gi Shyu and Hang Chang and Isner, {Jeffrey M.}",
year = "2003",
month = "6",
day = "20",
doi = "10.1016/S0024-3205(03)00318-7",
language = "English",
volume = "73",
pages = "563--579",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia

AU - Shyu, Kou-Gi

AU - Chang, Hang

AU - Isner, Jeffrey M.

PY - 2003/6/20

Y1 - 2003/6/20

N2 - Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation of the external iliac artery and the excision of the common and superficial femoral artery in one female WHHL rabbit, 250 μg of phVEGF165 (n = 8), 500 μg of pAng1* (n = 8), or 250 μg of phVEGF165 plus 500 μg of pAng1* (n = 8) was injected intramuscularly into the ischemic hindlimb muscles. Gross appearance of ischemic limb, collateral vessel formation and limb perfusion were assessed 30 days after treatment. The incidence of ischemic limb necrosis was higher in the animals treated by phVEGF165 or by pAng1* than in those treated by phVEGF165 plus pAng1* (100%, 75% and 14.3%, respectively; P = 0.002). Animals in the combination therapy group had a significantly higher calf blood pressure ratio at day 30 (VEGF plus Ang1* = 0.84 ± 0.06; VEGF = 0.54 ± 0.01; Ang1* = 0.59 ± 0.05; P <0.01). A combination therapy of VEGF plus Ang*1 had a significantly higher (P <0.01) angiographic score than either therapy alone. Capillary density (P <0.05) and capillary/muscle fiber ratio (P <0.01) of the combination therapy group were also significantly higher than that of either therapy alone. In conclusion, Ang1 can potentiate the angiogenic response to VEGF in the hyperlipidemic rabbit model of acute hindlimb ischemia. Intramuscular administration of cytokines on revascularization of the ischemic hindlimb model of hyperlipidemic rabbit is feasible.

AB - Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation of the external iliac artery and the excision of the common and superficial femoral artery in one female WHHL rabbit, 250 μg of phVEGF165 (n = 8), 500 μg of pAng1* (n = 8), or 250 μg of phVEGF165 plus 500 μg of pAng1* (n = 8) was injected intramuscularly into the ischemic hindlimb muscles. Gross appearance of ischemic limb, collateral vessel formation and limb perfusion were assessed 30 days after treatment. The incidence of ischemic limb necrosis was higher in the animals treated by phVEGF165 or by pAng1* than in those treated by phVEGF165 plus pAng1* (100%, 75% and 14.3%, respectively; P = 0.002). Animals in the combination therapy group had a significantly higher calf blood pressure ratio at day 30 (VEGF plus Ang1* = 0.84 ± 0.06; VEGF = 0.54 ± 0.01; Ang1* = 0.59 ± 0.05; P <0.01). A combination therapy of VEGF plus Ang*1 had a significantly higher (P <0.01) angiographic score than either therapy alone. Capillary density (P <0.05) and capillary/muscle fiber ratio (P <0.01) of the combination therapy group were also significantly higher than that of either therapy alone. In conclusion, Ang1 can potentiate the angiogenic response to VEGF in the hyperlipidemic rabbit model of acute hindlimb ischemia. Intramuscular administration of cytokines on revascularization of the ischemic hindlimb model of hyperlipidemic rabbit is feasible.

KW - Angiopoietin-1

KW - Collateral circulation

KW - Growth substances

KW - Hypercholesterolemia

KW - Peripheral vascular disease

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=0037721109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037721109&partnerID=8YFLogxK

U2 - 10.1016/S0024-3205(03)00318-7

DO - 10.1016/S0024-3205(03)00318-7

M3 - Article

VL - 73

SP - 563

EP - 579

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 5

ER -