石灰化大動脈弁疾患におけるエピジェネティック制御：メカニズムと治療の可能性

Calcific aortic valve disease (CAVD) is a progressive cardiovascular disorder pathologically defined by valvular sclerosis, fibrosis, and ectopic mineralization, which constitutes a substantial and growing public health burden. Currently, surgical intervention represents the sole effective treatment, underscoring a critical unmet need for novel pharmacological strategies that can halt disease progression or provide early therapeutic intervention. Extensive research has established that the pathogenesis of CAVD is driven by a complex interplay of multiple mechanisms including inflammatory responses, oxidative stress, and metabolic dysregulation which are intricately modulated by epigenetic regulation, post-transcriptional modifications, and protein post-translational modifications. In recent years, the field of epigenetics has garnered considerable attention, particularly for its pivotal role in the pathogenesis of oncological and cardiovascular diseases and the subsequent development of targeted therapeutic strategies. Consequently, numerous investigations have been dedicated to elucidating the involvement of epigenetic mechanisms in CAVD, encompassing DNA methylation, histone modifications (including methylation and acetylation), and RNA methylation, with a pronounced emphasis on the regulatory functions of non-coding RNAs. This review synthesizes recent advances in our understanding of epigenetic mechanisms underlying CAVD, with a specific focus on the role of RNA N6-methyladenosine (m6A) methylation, and highlights the pivotal significance of epigenetic modulation in critical biological processes and CAVD pathogenesis. Collectively, these findings offer valuable mechanistic insights and may illuminate novel paths toward the clinical translation of epigenetically targeted therapies for CAVD.