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

## TL;DR

Propofol reduces blood vessel growth by triggering endoplasmic reticulum stress, which suppresses a key transcription factor involved in VEGFA production.

## Contribution

The study reveals a novel mechanism by which propofol inhibits angiogenesis through the PERK/eIF2α/TFAP2C pathway.

## Key findings

- Propofol activates endoplasmic reticulum stress, suppressing TFAP2C translation.
- TFAP2C binds to the VEGFA promoter to regulate its transcription.
- Propofol inhibits VEGFA/VEGFR2-dependent angiogenesis in vitro and in vivo.

## 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.

Schematic representation of the mechanism of propofol inhibition of VEGFA/VEGFR2-associated angiogenesis via the PERK/eIF2α/TFAP2C axis.

The online version contains supplementary material available at 10.1007/s10495-025-02214-w.