Epigenetic mechanisms in aneurysm formation, growth, and rupture: A systematic review

IntroductionIntracranial aneurysms (IAs) affect approximately 3.2% of the global population, and their rupture leading to subarachnoid hemorrhage remains a significant cause of morbidity and mortality despite therapeutic advancements. While genetic factors have been implicated in IA pathogenesis, they account for only about 41% of heritability, suggesting that other mechanisms-particularly epigenetic modifications-may play a critical role. Epigenetic processes such as DNA methylation, histone modification, and non-coding RNA regulation have been shown to mediate gene-environment interactions, influencing endothelial function and vascular remodeling. This systematic review aims to synthesize the current literature on epigenetic mechanisms implicated in IA development, progression, and rupture.MethodsThe review was conducted in accordance with PRISMA guidelines, including both in vitro and in vivo studies available in PubMed up to November 2023. A total of 1019 studies were screened, resulting in 77 eligible full-text articles for data extraction.ResultsThe most frequently studied mechanisms were microRNAs (59.7%), DNA/RNA methylation (20.8%), circular RNAs (7.8%), long non-coding RNAs (6.5%), and histone modifications (5.2%). Notably, only three overlapping epigenetic targets were identified across studies, underscoring the field's methodological heterogeneity and lack of standardization. These individual epigenetic pathways are further examined in detail within the Discussion section.ConclusionThese findings underscore the emerging role of epigenetic research in elucidating novel pathways of intracranial aneurysm pathogenesis, while the limited reproducibility across studies highlights the need for standardized methodologies and larger, more diverse cohorts. Epigenetic regulation remains a promising target for future genetic and therapeutic investigations.