Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway

Drug Des Devel Ther. 2023 May 24:17:1567-1582. doi: 10.2147/DDDT.S403134. eCollection 2023.

Abstract

Purpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury.

Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay.

Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury.

Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.

Keywords: Paeonol; VEGFR2; c-Myc; reendothelialization; vascular injury.

MeSH terms

  • Animals
  • Carotid Artery Injuries* / drug therapy
  • Carotid Artery Injuries* / pathology
  • Cells, Cultured
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Mice
  • Molecular Docking Simulation
  • Signal Transduction
  • Vascular System Injuries* / drug therapy
  • Vascular System Injuries* / metabolism

Substances

  • paeonol

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81741007, 81870363]; the science & technology departments of Sichuan province [grant number 2020JDTD0025]; and the Chengdu University of Traditional Chinese Medicine [grant number 008066, 030038199, BJRC2018001/030041023, 030041224, ZKYY2004/030055180, and 242030016].