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

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cell Signaling

Background:

• Vascular restenosis is a significant complication after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG).
• The mammalian target of rapamycin (mTOR) kinase is implicated in cell proliferation and apoptosis, making it a target for restenosis treatment.
• Rapamycin (RAPA), an mTOR inhibitor, can reduce restenosis but may also impair normal vascular endothelial cell function via mTOR/VEGF signaling.

Purpose of the Study:

• To elucidate the mechanism by which RAPA affects vascular endothelial cell proliferation.
• To investigate the role of the mTOR/AP-1/VEGF pathway in regulating vascular endothelial cell growth and restenosis.

Main Methods:

• Inhibition and overexpression of endogenous mTOR, AP-1, and VEGF in cellular models.
• Treatment with rapamycin (RAPA) and AP-1 siRNA to assess effects on cell proliferation.
• Analysis of the mTOR/AP-1/VEGF signaling axis.

Main Results:

• Inhibition of AP-1 or mTOR decreased vascular endothelial cell proliferation.
• Upregulation of AP-1 or mTOR increased cell proliferation.
• VEGF overexpression enhanced cell proliferation, whereas RAPA-induced mTOR inhibition reduced it.

Conclusions:

• The mTOR/AP-1/VEGF pathway is crucial for regulating vascular endothelial cell growth.
• Combining mTOR downregulation with VEGF upregulation may offer a dual benefit: inhibiting restenosis and maintaining normal vascular cell function post-PCI/CABG.