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Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization.
Circulation. 2004 May 25; 109(20):2454-61.Circ

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.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, JapanNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15148275

Citation

Hiasa, Ken-ichi, et al. "Gene Transfer of Stromal Cell-derived Factor-1alpha Enhances Ischemic Vasculogenesis and Angiogenesis Via Vascular Endothelial Growth Factor/endothelial Nitric Oxide Synthase-related Pathway: Next-generation Chemokine Therapy for Therapeutic Neovascularization." Circulation, vol. 109, no. 20, 2004, pp. 2454-61.
Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation. 2004;109(20):2454-61.
Hiasa, K., Ishibashi, M., Ohtani, K., Inoue, S., Zhao, Q., Kitamoto, S., Sata, M., Ichiki, T., Takeshita, A., & Egashira, K. (2004). Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation, 109(20), 2454-61.
Hiasa K, et al. Gene Transfer of Stromal Cell-derived Factor-1alpha Enhances Ischemic Vasculogenesis and Angiogenesis Via Vascular Endothelial Growth Factor/endothelial Nitric Oxide Synthase-related Pathway: Next-generation Chemokine Therapy for Therapeutic Neovascularization. Circulation. 2004 May 25;109(20):2454-61. PubMed PMID: 15148275.
* Article titles in AMA citation format should be in sentence-case
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: next-generation chemokine therapy for therapeutic neovascularization. AU - Hiasa,Ken-ichi, AU - Ishibashi,Minako, AU - Ohtani,Kisho, AU - Inoue,Shujiro, AU - Zhao,Qingwei, AU - Kitamoto,Shiro, AU - Sata,Masataka, AU - Ichiki,Toshihiro, AU - Takeshita,Akira, AU - Egashira,Kensuke, Y1 - 2004/05/17/ PY - 2004/5/19/pubmed PY - 2004/10/14/medline PY - 2004/5/19/entrez SP - 2454 EP - 61 JF - Circulation JO - Circulation VL - 109 IS - 20 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15148275/Gene_transfer_of_stromal_cell_derived_factor_1alpha_enhances_ischemic_vasculogenesis_and_angiogenesis_via_vascular_endothelial_growth_factor/endothelial_nitric_oxide_synthase_related_pathway:_next_generation_chemokine_therapy_for_therapeutic_neovascularization_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000128213.96779.61?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -