Edaravone targets PDGFRβ to attenuate VSMC phenotypic transition
Xueqing Tang1, Dannya Estau2, Xiaoru Huang2
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Beijing Key Laboratory of Cardiovascular Receptors Research; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
Life Sciences
|March 20, 2025
Summary
Edaravone (EDA) targets PDGFRβ, effectively inhibiting vascular smooth muscle cell (VSMC) transition implicated in cardiovascular diseases. This repurposed drug offers a new therapeutic avenue for VSMC-related conditions.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Cellular Signaling
Background:
- Platelet-derived growth factor receptor beta (PDGFRβ)-driven vascular smooth muscle cell (VSMC) phenotypic transition is a key factor in cardiovascular diseases.
- Current interventions for this pathological process are limited.
Purpose of the Study:
- To identify and investigate a potential drug targeting PDGFRβ for the treatment of VSMC phenotypic transition.
- To explore the efficacy and mechanism of edaravone (EDA) in modulating VSMC phenotype.
Main Methods:
- Connectivity Map (CMAP) analysis to identify potential drugs.
- In vitro cell models and in vivo mouse models of vascular injury.
- Molecular docking, DRATS, and CETSA to confirm drug-target interaction.
- Assessment of VSMC phenotypic markers and downstream signaling pathways (AKT, ERK1/2).
Main Results:
- Edaravone (EDA) was identified as a potential drug targeting PDGFRβ.
- EDA significantly suppressed PDGFRβ-mediated VSMC phenotypic transition and reduced neointimal hyperplasia in injured arteries.
- EDA directly interacts with PDGFRβ, inhibiting its downstream signaling pathways.
Conclusions:
- Edaravone (EDA) is a repurposed drug that targets PDGFRβ to attenuate VSMC phenotypic transition.
- EDA presents a promising therapeutic strategy for cardiovascular diseases driven by VSMC phenotypic transition.
