Epigenetic Biomarkers in Thoracic Aortic Aneurysm, Dissection, and Bicuspid Aortopathy: A Comprehensive Review.

Thoracic aortic disease (TAD) encompasses a spectrum of life-threatening conditions, including thoracic aortic aneurysm (TAA), acute type A aortic dissection (ATAAD), and bicuspid aortic valve (BAV)-associated aortopathy. While genetic mutations are well-documented contributors, emerging evidence highlights epigenetic mechanisms as critical regulators of TAD pathogenesis. This comprehensive review explores the role of epigenetic modifications-DNA methylation, histone modifications, and microRNA (miRNA) regulation-in vascular remodeling, extracellular matrix degradation, and endothelial dysfunction. Aberrant DNA methylation patterns have been implicated in TAA and ATAAD, influencing genes responsible for vascular integrity and inflammation. Histone modifications modulate smooth muscle cell phenotype switching, impacting aneurysm progression. Additionally, dysregulated miRNA expression contributes to endothelial barrier disruption and extracellular matrix remodeling, presenting novel avenues for biomarker discovery. The reversibility of epigenetic modifications offers a promising therapeutic target, with pharmacological agents such as histone deacetylase inhibitors and miRNA-based therapies showing potential in preclinical models. This review underscores the translational potential of epigenetic biomarkers for early disease detection, risk stratification, and precision medicine approaches. Further research is needed to integrate these findings into clinical practice, paving the way for innovative diagnostic and therapeutic strategies in TAD management.