Research Papers:

The mTOR/AP-1/VEGF signaling pathway regulates vascular endothelial cell growth

Shuo Wang, Jiawei Lu, Qingsheng You, Hua Huang, Yingying Chen and Kun Liu _

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Oncotarget. 2016; 7:53269-53276. https://doi.org/10.18632/oncotarget.10756

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Shuo Wang1,2, Jiawei Lu1, Qingsheng You2, Hua Huang3, Yingying Chen4, Kun Liu2

1Medical College, Nantong University, Nantong, China

2Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China

3Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China

4Department of Immunology, Nantong University, Nantong, China

Correspondence to:

Kun Liu, email: ntliukun@163.com

Keywords: mTOR, AP-1, VEGF, vascular endothelial cell, signaling pathway

Received: April 20, 2016     Accepted: July 10, 2016     Published: July 21, 2016


Vascular restenosis is a common adverse event following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The atypical Ser/Thr protein kinase mammalian target of rapamycin (mTOR) plays an important role in cell differentiation and apoptosis. Vascular restenosis caused by excessive endothelial cell proliferation can be inhibited by local application of the mTOR inhibitor rapamycin (RAPA); however, RAPA can also suppress normal vascular endothelial cell growth by blocking mTOR/VEGF signaling, although the underlying mechanism is still unclear. Here, endogenous mTOR, AP-1, and VEGF were inhibited or overexpressed to investigate the mechanism underlying the effects of RAPA. Inhibition of AP-1 or mTOR with AP-1-siRNA or RAPA treatment respectively, decreased vascular endothelial cell proliferation, upregulation of AP-1 or mTOR increased cell proliferation, and VEGF overexpression increased, while RAPA-induced mTOR inhibition decreased vascular endothelial cell proliferation, the results indicate that combining mTOR downregulation and VEGF upregulation might both inhibit restenosis and maintain normal vascular endothelial cell growth after PCI or CABG, suggest the mTOR/AP-1/VEGF pathway might play a crucial role in regulating vascular endothelial cell growth.

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