Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway

Qingwei Zhao

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1alpha gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. METHODS AND RESULTS: To examine SDF-1alpha-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express beta-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1alpha or empty plasmids into the ischemic muscles. SDF-1alpha gene transfer mobilized EPCs into the peripheral blood, augmented recovery of blood perfusion to the ischemic limb, and increased capillary density associated with partial incorporation of LacZ-positive cells into the capillaries of the ischemic limb, suggesting that SDF-1alpha induced vasculogenesis and angiogenesis. SDF-1alpha gene transfer did not affect ischemia-induced expression of vascular endothelial growth factor (VEGF) but did enhance Akt and endothelial nitric oxide synthase (eNOS) activity. Blockade of VEGF or NOS prevented all such SDF-1alpha-induced effects. CONCLUSIONS: SDF-1alpha gene transfer enhanced ischemia-induced vasculogenesis and angiogenesis in vivo through a VEGF/eNOS-related pathway. This strategy might become a novel chemokine therapy for next generation therapeutic neovascularization.
Original languageEnglish
Pages (from-to)2454-2461
JournalCirculatioin
Volume109
StatePublished - May 25 2004

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Chemokine CXCL12
Nitric Oxide Synthase Type III
Vascular Endothelial Growth Factor A
Genes
Chemokines
Ischemia
Plasmids
Extremities
Hindlimb
beta-Galactosidase
Blood Cells
Therapeutics
Perfusion
Bone Marrow
Muscles

Cite this

@article{e3020de8af314b85b818acb8384dbcea,
title = "Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway",
abstract = "BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1alpha gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. METHODS AND RESULTS: To examine SDF-1alpha-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express beta-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1alpha or empty plasmids into the ischemic muscles. SDF-1alpha gene transfer mobilized EPCs into the peripheral blood, augmented recovery of blood perfusion to the ischemic limb, and increased capillary density associated with partial incorporation of LacZ-positive cells into the capillaries of the ischemic limb, suggesting that SDF-1alpha induced vasculogenesis and angiogenesis. SDF-1alpha gene transfer did not affect ischemia-induced expression of vascular endothelial growth factor (VEGF) but did enhance Akt and endothelial nitric oxide synthase (eNOS) activity. Blockade of VEGF or NOS prevented all such SDF-1alpha-induced effects. CONCLUSIONS: SDF-1alpha gene transfer enhanced ischemia-induced vasculogenesis and angiogenesis in vivo through a VEGF/eNOS-related pathway. This strategy might become a novel chemokine therapy for next generation therapeutic neovascularization.",
author = "Qingwei Zhao",
year = "2004",
month = "5",
day = "25",
language = "English",
volume = "109",
pages = "2454--2461",
journal = "Circulatioin",

}

TY - JOUR

T1 - Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway

AU - Zhao, Qingwei

PY - 2004/5/25

Y1 - 2004/5/25

N2 - BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1alpha gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. METHODS AND RESULTS: To examine SDF-1alpha-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express beta-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1alpha or empty plasmids into the ischemic muscles. SDF-1alpha gene transfer mobilized EPCs into the peripheral blood, augmented recovery of blood perfusion to the ischemic limb, and increased capillary density associated with partial incorporation of LacZ-positive cells into the capillaries of the ischemic limb, suggesting that SDF-1alpha induced vasculogenesis and angiogenesis. SDF-1alpha gene transfer did not affect ischemia-induced expression of vascular endothelial growth factor (VEGF) but did enhance Akt and endothelial nitric oxide synthase (eNOS) activity. Blockade of VEGF or NOS prevented all such SDF-1alpha-induced effects. CONCLUSIONS: SDF-1alpha gene transfer enhanced ischemia-induced vasculogenesis and angiogenesis in vivo through a VEGF/eNOS-related pathway. This strategy might become a novel chemokine therapy for next generation therapeutic neovascularization.

AB - BACKGROUND: Stromal cell-derived factor-1alpha (SDF-1alpha) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1alpha gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. METHODS AND RESULTS: To examine SDF-1alpha-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express beta-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1alpha or empty plasmids into the ischemic muscles. SDF-1alpha gene transfer mobilized EPCs into the peripheral blood, augmented recovery of blood perfusion to the ischemic limb, and increased capillary density associated with partial incorporation of LacZ-positive cells into the capillaries of the ischemic limb, suggesting that SDF-1alpha induced vasculogenesis and angiogenesis. SDF-1alpha gene transfer did not affect ischemia-induced expression of vascular endothelial growth factor (VEGF) but did enhance Akt and endothelial nitric oxide synthase (eNOS) activity. Blockade of VEGF or NOS prevented all such SDF-1alpha-induced effects. CONCLUSIONS: SDF-1alpha gene transfer enhanced ischemia-induced vasculogenesis and angiogenesis in vivo through a VEGF/eNOS-related pathway. This strategy might become a novel chemokine therapy for next generation therapeutic neovascularization.

M3 - Article

VL - 109

SP - 2454

EP - 2461

JO - Circulatioin

JF - Circulatioin

ER -