# Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential

## TL;DR

This paper reviews how chromatin remodeling controls vascular smooth muscle cell changes linked to vascular diseases and explores its potential for new therapies.

## Contribution

The paper provides a comprehensive review of recent advances in chromatin remodeling's role in vascular smooth muscle cell phenotypic switching.

## Key findings

- Chromatin remodeling translates mechanical and inflammatory signals into epigenetic changes in vascular smooth muscle cells.
- ATP-dependent chromatin remodelers and modifying enzymes regulate gene expression during VSMC phenotypic switching.
- Targeting chromatin remodelers shows translational potential for treating vascular remodeling diseases.

## Abstract

Vascular remodeling is a characteristic pathological feature of various vascular diseases, including atherosclerosis, restenosis following vascular injury, hypertension, and aneurysms. The phenotypic switching of vascular smooth muscle cells (VSMCs) acts as a key driver of vascular remodeling. Under specific pathological stimuli, VSMCs rapidly transition from a contractile to a dedifferentiated phenotype, characterized by enhanced proliferation, migration, and secretory activity. Chromatin remodeling, a core mechanism of epigenetic regulation, orchestrates dynamic changes in chromatin structure and function through ATP-dependent remodeling complexes, histone-modifying enzymes, and DNA methyltransferases. These components collectively translate mechanical stress, metabolic disturbances, and inflammatory signals into reversible epigenetic modifications, thereby precisely regulating VSMC phenotypic switching. As such, chromatin remodeling represents a critical node for therapeutic intervention in vascular remodeling-related diseases. In recent years, a growing body of research has focused on the role of chromatin remodelers in regulating VSMC phenotype. In this review, we focus on the roles of ATP-dependent chromatin-remodeling factors and chromatin-modifying enzymes in the control of gene expression of VSMC phenotype switching. Firstly, we summarize the latest insights into chromatin remodeling and VSMC phenotypic switching, and then discuss recent advances in the identification and functional characterization of chromatin remodeling molecules, emphasizing their implications for VSMC behavior. Finally, we highlight the translational potential of targeting chromatin remodelers in the development of clinical therapies for vascular remodeling diseases and outline future directions for research in this field.