Cell death constitutes a critical component of the pathophysiology of cardiovascular diseases. A growing array of non-apoptotic forms of regulated cell death (RCD)—such as necroptosis, ferroptosis, pyroptosis, and cuproptosis—has been identified and is intimately linked to various cardiovascular conditions. These forms of RCD are governed by genetically programmed mechanisms within the cell, with epigenetic modifications being a common and crucial regulatory method. Such modifications include DNA methylation, RNA methylation, histone methylation, histone acetylation, and non-coding RNAs. This review recaps the roles of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs in cardiovascular diseases, as well as the mechanisms by which epigenetic modifications regulate key proteins involved in cell death. Furthermore, we systematically catalog the existing epigenetic pharmacological agents targeting novel forms of RCD and their mechanisms of action in cardiovascular diseases. This article aims to underscore the pivotal role of epigenetic modifications in precisely regulating specific pathways of novel RCD in cardiovascular diseases, thus offering potential new therapeutic avenues that may prove more effective and safer than traditional treatments.

中文翻译：

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心血管疾病中多种受调节细胞死亡方式的表观遗传调控：深入了解坏死性凋亡、细胞焦亡、铁死亡和铜死亡


细胞死亡是心血管疾病病理生理学的重要组成部分。越来越多的非凋亡形式的调节性细胞死亡（RCD）——例如坏死性凋亡、铁死亡、细胞焦亡和铜凋亡——已被鉴定出来，并且与各种心血管疾病密切相关。这些形式的 RCD 受细胞内遗传编程机制的控制，表观遗传修饰是一种常见且关键的调节方法。此类修饰包括 DNA 甲基化、RNA 甲基化、组蛋白甲基化、组蛋白乙酰化和非编码 RNA。这篇综述回顾了 DNA 甲基化、RNA 甲基化、组蛋白修饰和非编码 RNA 在心血管疾病中的作用，以及表观遗传修饰调节参与细胞死亡的关键蛋白质的机制。此外，我们系统地对现有的针对新型 RCD 的表观遗传药物及其在心血管疾病中的作用机制进行了分类。本文旨在强调表观遗传修饰在精确调节心血管疾病中新型 RCD 特定途径中的关键作用，从而提供潜在的新治疗途径，可能比传统治疗更有效、更安全。