Formononetin Alleviates the Inflammatory Response Induced by Carotid Balloon Injury in Rats via the PP2A/MAPK Axis

Area of Science:

• Vascular Biology
• Pharmacology
• Biochemistry

Background:

• Carotid arteriosclerosis necessitates interventional therapy, but restenosis and poor stent patency remain significant challenges.
• Vascular inflammation, mediated by MAPK and PP2A pathways, is a key factor limiting treatment success.
• Formononetin (FOR) presents a potential therapeutic strategy by targeting these inflammatory pathways.

Purpose of the Study:

• To investigate the efficacy of Formononetin (FOR) in mitigating vascular damage and inflammation post-carotid artery balloon injury (CABI).
• To elucidate the underlying molecular mechanisms involving the PP2A/MAPK signaling axis in FOR's therapeutic effects.

Main Methods:

• A rat model of CABI was established, with groups receiving varying FOR concentrations.
• Vascular integrity and inflammation were assessed using histological (HE staining) and molecular techniques (ELISA, Western blot, immunohistochemistry).
• Human umbilical vein endothelial cells (HUVECs) were used in vitro to further examine FOR's effects on MAPK and PP2A signaling.

Main Results:

• FOR treatment significantly reduced carotid lumen narrowing and tissue damage in the CABI model.
• FOR administration led to decreased levels of inflammatory cytokines (IL-6, TNF-α) and modulated PP2A/MAPK signaling.
• Specifically, FOR reversed PP2A downregulation, increased MAPK expression, and reduced ERK1/2 phosphorylation.

Conclusions:

• Formononetin (FOR) effectively reduces vascular damage and inflammation after CABI, primarily through the PP2A/MAPK signaling pathway.
• FOR promotes vascular remodeling and restores protein expression, indicating its potential as a therapeutic agent for vascular injuries.