# A Comprehensive Review of Epigenetic Regulation of Vascular Smooth Muscle Cells During Development and Disease

## TL;DR

This review discusses how epigenetic changes control vascular smooth muscle cells during development and how they contribute to cardiovascular diseases.

## Contribution

The paper provides a comprehensive overview of epigenetic regulation in vascular smooth muscle cells during both health and disease.

## Key findings

- Epigenetic mechanisms like DNA methylation and histone modifications regulate vascular smooth muscle cell identity.
- Phenotypic plasticity of these cells is linked to vascular remodeling and disease progression.
- Understanding these epigenetic processes could lead to new insights into vascular development and treatment strategies.

## Abstract

Vascular smooth muscle cells (VSMCs) in the tunica media are essential for maintaining the structure and function of the arterial wall. These cells regulate vascular tone and contribute to vasculogenesis and angiogenesis, particularly during development. Proper control of VSMC differentiation ensures the correct size and patterning of vessels. Dysregulation of VSMC behaviour in adulthood, however, is linked to serious cardiovascular diseases, including aortic aneurysm, coronary artery disease, atherosclerosis and pulmonary hypertension. VSMCs are characterised by their phenotypic plasticity, which is the capacity to transition from a contractile to a synthetic, dedifferentiated state in response to environmental cues. This phenotypic switch plays a central role in vascular remodelling, a process that drives the progression of many vascular pathologies. Epigenetic mechanisms, which are defined as heritable but reversible changes in gene expression that do not involve alterations to the DNA sequence, have emerged as key regulators of VSMC identity and behaviour. These mechanisms include DNA methylation, histone modifications, chromatin remodelling, non-coding RNA and RNA modifications. Understanding how these epigenetic processes influence VSMC plasticity is crucial to uncovering the molecular basis of vascular development and disease. This review explores the current understanding of VSMC biology, focusing on epigenetic regulation in health and pathology.