Gene transfer of stromal cell-derived factor-1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: Next-generation chemokine therapy for therapeutic neovascularization

Hiasa Ken-Ichi, Minako Ishibashi, kisho ohtani, Shuujirou Inoue, Qingwei Zhao, Shiro Kitamoto, Masataka Sata, Toshihiro Ichiki, Akira Takeshita, Kensuke Egashira

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277 Citations (Scopus)

Abstract

Background-Stromal cell-derived factor-1α (SDF-1α) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1α gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. Methods and Results-To examine SDF-1α-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express β-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1α or empty plasmids into the ischemic muscles. SDF-1α 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-1α induced vasculogenesis and angiogenesis. SDF-1α 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-1α-induced effects. Conclusions-SDF-1α 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
Number of pages8
JournalCirculation
Volume109
Issue number20
DOIs
Publication statusPublished - May 25 2004

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

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gene transfer of stromal cell-derived factor-1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway : Next-generation chemokine therapy for therapeutic neovascularization. / Ken-Ichi, Hiasa; Ishibashi, Minako; ohtani, kisho; Inoue, Shuujirou; Zhao, Qingwei; Kitamoto, Shiro; Sata, Masataka; Ichiki, Toshihiro; Takeshita, Akira; Egashira, Kensuke.

In: Circulation, Vol. 109, No. 20, 25.05.2004, p. 2454-2461.

Research output: Contribution to journalArticle

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abstract = "Background-Stromal cell-derived factor-1α (SDF-1α) is implicated as a chemokine for endothelial progenitor cells (EPCs). We therefore hypothesized that SDF-1α gene transfer would induce therapeutic neovascularization in vivo by functioning as a chemokine of EPC. Methods and Results-To examine SDF-1α-induced mobilization of EPC, we used bone marrow-transplanted mice whose blood cells ubiquitously express β-galactosidase (LacZ). We produced unilateral hindlimb ischemia in the mice and transfected them with plasmid DNA encoding SDF-1α or empty plasmids into the ischemic muscles. SDF-1α 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-1α induced vasculogenesis and angiogenesis. SDF-1α 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-1α-induced effects. Conclusions-SDF-1α 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.",
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AU - Ishibashi, Minako

AU - ohtani, kisho

AU - Inoue, Shuujirou

AU - Zhao, Qingwei

AU - Kitamoto, Shiro

AU - Sata, Masataka

AU - Ichiki, Toshihiro

AU - Takeshita, Akira

AU - Egashira, Kensuke

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