Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is a progressive vascular disorder closely associated with the phenotypic transformation of vascular smooth muscle cells (VSMCs). Histone modifications-including acetylation, methylation, phosphorylation, lactylation, succinylation, ubiquitination, and small ubiquitin-like modifier modification-play pivotal roles in regulating chromatin accessibility, gene expression, and cellular behavior during this transformation. These epigenetic marks influence VSMCs proliferation, migration, apoptosis, and inflammatory responses, thereby contributing to AAA development and progression. This review systematically summarizes the molecular mechanisms by which histone modifications regulate VSMCs phenotypes and explores emerging therapeutic strategies that target epigenetic regulators such as histone deacetylases, histone methyltransferases, and lactate dehydrogenase A. Furthermore, this study highlights the potential of spatial omics and CRISPR-dCas9 epigenome editing tools for deciphering and modulating VSMC states with spatial and cell type precision. Advancing our understanding of these regulatory networks may pave the way for novel, individualized interventions in AAA treatment.