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Article Open Access

RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells

  • Authors:
    • Yanhua Liu
    • Jin Zou
    • Bingong Li
    • Yuqin Wang
    • Delong Wang
    • Yanqin Hao
    • Xuan Ke
    • Xingxing Li
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiology, Loudi Central Hospital, Loudi, Hunan 417000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 65-74
    |
    Published online on: May 22, 2017
       https://doi.org/10.3892/ijmm.2017.2998
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Abstract

Endothelial-mesenchymal transition (EndMT) is an essential mechanism in the cardiovascular system, for both cardiovascular development and cardiovascular diseases (CVDs). Recent studies indicate that runt-related transcription factor 3 (RUNX3) contributes to EndMT and endothelial cell dysfunction. However, the underlying molecular mechanism remains unknown. The present study was designed to investigate the role of RUNX3 in EndMT and endothelial cell function, and to elucidate the underlying molecular mechanism. Human cardiac microvascular endothelial cells (HCMECs) were incubated in strictly controlled hypoxic conditions (1% O2). HCMECs were cultured under normoxic conditions (21% O2), and then moved to a strictly controlled hypoxic environment (1% O2). Under this hypoxic condition, the cells were transfected with the lentiviral vector containing RUNX3 or an empty lentiviral vector for 8 h. After the cells were cultured under hypoxic conditions for 4 days, CD31 and α-smooth muscle actin colocalization were assessed by immunofluorescence microscopy. Transwell migration and tube formation assays were used to examine the migration and angiogenesis ability. RT-qPCR and western blotting were used to determine the expression of molecules involved in EndMT. Hypoxia induced the transition of HCMECs to mesenchymal cells and markedly promoted tube formation and cell migration. Transforming growth factor-β (TGF-β) and Notch signaling were activated during the hypoxia-induced EndMT of HCMECs. RUNX3 knockdown attenuated EndMT of HCMECs, promoted angiogenic phenotype, and reduced endothelial cell migration. In conclusion, our results showed that RUNX3 knockdown attenuated hypoxia-induced EndMT and reversed endothelial cell functions. RUNX3 is a common downstream target of TGF-β and Notch signaling, and may be a novel therapeutic target for treating CVD mediated by EndMT.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Zou J, Li B, Wang Y, Wang D, Hao Y, Ke X and Li X: RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. Int J Mol Med 40: 65-74, 2017.
APA
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y. ... Li, X. (2017). RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. International Journal of Molecular Medicine, 40, 65-74. https://doi.org/10.3892/ijmm.2017.2998
MLA
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y., Ke, X., Li, X."RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells". International Journal of Molecular Medicine 40.1 (2017): 65-74.
Chicago
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y., Ke, X., Li, X."RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells". International Journal of Molecular Medicine 40, no. 1 (2017): 65-74. https://doi.org/10.3892/ijmm.2017.2998
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Zou J, Li B, Wang Y, Wang D, Hao Y, Ke X and Li X: RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. Int J Mol Med 40: 65-74, 2017.
APA
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y. ... Li, X. (2017). RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. International Journal of Molecular Medicine, 40, 65-74. https://doi.org/10.3892/ijmm.2017.2998
MLA
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y., Ke, X., Li, X."RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells". International Journal of Molecular Medicine 40.1 (2017): 65-74.
Chicago
Liu, Y., Zou, J., Li, B., Wang, Y., Wang, D., Hao, Y., Ke, X., Li, X."RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells". International Journal of Molecular Medicine 40, no. 1 (2017): 65-74. https://doi.org/10.3892/ijmm.2017.2998
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