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Article

Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium

  • Authors:
    • Hong Huang
    • Feng Huang
    • Jian‑Ping Huang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiothoracic Surgery, The First People's Hospital of Nanning, Nanning, Guangxi 530022, P.R. China, Department of Emergency, The First People's Hospital of Nanning, Nanning, Guangxi 530022, P.R. China, Alibaba Business College, Hangzhou Normal University, Hangzhou, Zhejiang 310036, P.R. China
  • Pages: 1556-1562
    |
    Published online on: August 28, 2013
       https://doi.org/10.3892/mmr.2013.1657
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Abstract

Delta‑like‑4 (Dll‑4) prevents excess angiogenic sprouting and promotes the formation of a well‑differentiated vascular network. Therefore, transplantation of Dll‑4‑overexpressing endothelial progenitor cells (EPCs) was hypothesized to be superior to transplantation of EPCs in the treatment of ischemic heart disease. In the current study, EPCs harvested from C57BL/6 mouse bone marrow were infected in vitro with Dll‑4 (EPCDll‑4+) or Dll‑4 knockdown (EPCDll‑4‑) with recombinant lentiviral vectors and the control cells were non‑transfected or transduced with mock vectors (EPCnull). Eight‑week‑old C57BL/6 mice underwent ligation of the left anterior descending artery to establish a myocardial infarction (MI) model. The ligated animals were randomly divided into 5 groups, which, following one week, were intravenously injected with EPCs, EPCnull, EPCDll‑4+, EPCDll‑4‑ or medium. Two weeks later, echocardiographic assessment, western blotting, fluorescent microsphere and histological studies were performed. The results demonstrated that the number of mature vessels and blood flow in ischemic myocardium were increased in the EPCDll‑4+ group, but were markedly decreased in the EPCDll‑4‑ group compared with the control groups. The expression levels of Dll‑4, hairy/enhancer of split (Hes)‑related protein 1 (Hey‑1), phosphorylation of mammalian target of rapamycin (mTOR) and p70S6 kinase (p70S6K) were significantly increased in the EPCDll‑4+ group, while they were markedly decreased in the EPCDll‑4‑ group. Furthermore, for EPCDll‑4+‑treated animals, an enhanced cardiac function was observed as assessed by echocardiography. Thus, the transplantation of Dll‑4‑overexpressing EPCs stimulates neovascularization effectively, increases the blood flow to the ischemic zone and improves cardiac function. These effects may be due to the activation of Notch/Hey‑1/mTOR/p70S6K signaling pathways, which are initiated by Dll‑4.
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Copy and paste a formatted citation
Spandidos Publications style
Huang H, Huang F and Huang JP: Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium. Mol Med Rep 8: 1556-1562, 2013.
APA
Huang, H., Huang, F., & Huang, J. (2013). Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium. Molecular Medicine Reports, 8, 1556-1562. https://doi.org/10.3892/mmr.2013.1657
MLA
Huang, H., Huang, F., Huang, J."Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium". Molecular Medicine Reports 8.5 (2013): 1556-1562.
Chicago
Huang, H., Huang, F., Huang, J."Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium". Molecular Medicine Reports 8, no. 5 (2013): 1556-1562. https://doi.org/10.3892/mmr.2013.1657
Copy and paste a formatted citation
x
Spandidos Publications style
Huang H, Huang F and Huang JP: Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium. Mol Med Rep 8: 1556-1562, 2013.
APA
Huang, H., Huang, F., & Huang, J. (2013). Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium. Molecular Medicine Reports, 8, 1556-1562. https://doi.org/10.3892/mmr.2013.1657
MLA
Huang, H., Huang, F., Huang, J."Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium". Molecular Medicine Reports 8.5 (2013): 1556-1562.
Chicago
Huang, H., Huang, F., Huang, J."Transplantation of bone marrow‑derived endothelial progenitor cells overexpressing Delta‑like‑4 enhances functional neovascularization in ischemic myocardium". Molecular Medicine Reports 8, no. 5 (2013): 1556-1562. https://doi.org/10.3892/mmr.2013.1657
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