Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription

  • Apoptosis. 2026 Jan 12;31(1):42. doi: 10.1007/s10495-025-02214-w.
Fan Yang  1  2 ,  Yi Liu  1  2 ,  Hui Li  3 ,  Xue Shang  1  2 ,  Qing Hua  4 ,  Yun Zhu  5  6 ,  Beibei Tao  7 ,  Zhirong Sun  8  9
Affiliations
  • 1. Departmentof Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
  • 2. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong an Road, Shanghai, 200032, China.
  • 3. Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4. Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 5. Departmentof Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. [email protected].
  • 6. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong an Road, Shanghai, 200032, China. [email protected].
  • 7. Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China. [email protected].
  • 8. Departmentof Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. [email protected].
  • 9. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong an Road, Shanghai, 200032, China. [email protected].
PMID: 41524974 DOI: 10.1007/s10495-025-02214-w
Abstract

During anesthesia, significant hemodynamic changes often alter the vascular microenvironment and affecting endothelial cell behavior. Propofol, a commonly used intravenous anesthetic, has been widely studied for its role in tumor angiogenesis through tumor cell-derived VEGF-mediated endothelial interactions. However, its direct effects on endothelial cell-mediated angiogenesis in non-malignant diseases such as diabetic retinopathy, diabetic nephropathy, and coronary heart disease remain unclear. To address this gap, we examined the effects of propofol on VEGFA-mediated angiogenesis in vitro and in vivo. Mechanistically, propofol triggers endoplasmic reticulum stress by promoting phosphorylation of PERK and its downstream effector eIF2α, leading to suppressed translation of TFAP2C-a transcription factor critical for endothelial function. Further analysis revealed that TFAP2C directly binds to the VEGFA promoter to activate its transcription, thereby facilitating VEGFA/VEGFR2-dependent angiogenesis. Together, these findings not only broaden the understanding of propofol's pharmacological profile, but also identify TFAP2C as a novel transcriptional regulator of VEGFA, offering new perspectives for therapeutic targeting of VEGFA-mediated angiogenesis.

Keywords
Angiogenesis; Endoplasmic reticulum stress; Propofol; TFAP2C; Transcription factor; VEGFA/VEGFR2.
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