Magouliotis Dimitrios E, Sicouri Serge, Sicouri Noah, Baudo Massimo, Cabrucci Francesco, Yamashita Yoshiyuki, Ramlawi Basel
Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA 19096, USA.
Lankenau Medical Center, Wynnewood, PA 19096, USA.
Biomolecules. 2025 Apr 11;15(4):568. doi: 10.3390/biom15040568.
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.
胸主动脉疾病（TAD）包括一系列危及生命的病症，包括胸主动脉瘤（TAA）、急性A型主动脉夹层（ATAAD）以及二叶式主动脉瓣（BAV）相关的主动脉病变。虽然基因突变是有充分文献记载的致病因素，但新出现的证据表明表观遗传机制是TAD发病机制的关键调节因子。这篇综述全面探讨了表观遗传修饰——DNA甲基化、组蛋白修饰和微小RNA（miRNA）调控——在血管重塑、细胞外基质降解和内皮功能障碍中的作用。异常的DNA甲基化模式与TAA和ATAAD有关，影响负责血管完整性和炎症的基因。组蛋白修饰调节平滑肌细胞表型转换，影响动脉瘤进展。此外，miRNA表达失调导致内皮屏障破坏和细胞外基质重塑，为生物标志物发现提供了新途径。表观遗传修饰的可逆性提供了一个有前景的治疗靶点，诸如组蛋白去乙酰化酶抑制剂和基于miRNA的疗法等药物在临床前模型中显示出潜力。这篇综述强调了表观遗传生物标志物在疾病早期检测、风险分层和精准医学方法中的转化潜力。需要进一步研究将这些发现整合到临床实践中，为TAD管理中的创新诊断和治疗策略铺平道路。
