Center for Molecular Cardiology, University of Zürich, Zürich, Switzerland.
University Heart Center, Cardiology, University Hospital Zürich, Zürich, Switzerland.
Handb Exp Pharmacol. 2022;270:511-535. doi: 10.1007/164_2020_422.
Emerging evidence suggests the growing importance of "nongenetic factors" in the pathogenesis of atherosclerotic vascular disease. Indeed, the inherited genome determines only part of the risk profile as genomic approaches do not take into account additional layers of biological regulation by "epi"-genetic changes. Epigenetic modifications are defined as plastic chemical changes of DNA/histone complexes which critically affect gene activity without altering the DNA sequence. These modifications include DNA methylation, histone posttranslational modifications, and non-coding RNAs and have the ability to modulate gene expression at both transcriptional and posttranscriptional level. Notably, epigenetic signals are mainly induced by environmental factors (i.e., pollution, smoking, noise) and, once acquired, may be transmitted to the offspring. The inheritance of adverse epigenetic changes may lead to premature deregulation of pathways involved in vascular damage and endothelial dysfunction. Here, we describe the emerging role of epigenetic modifications as fine-tuners of gene transcription in atherosclerosis. Specifically, the following aspects are described in detail: (1) discovery and impact of the epigenome in cardiovascular disease, (2) the epigenetic landscape in atherosclerosis; (3) inheritance of epigenetic signals and premature vascular disease; (4) epigenetic control of lipid metabolism, vascular oxidative stress, inflammation, autophagy, and apoptosis; (5) epigenetic biomarkers in patients with atherosclerosis; (6) novel therapeutic strategies to modulate epigenetic marks. Understanding the individual epigenetic profile may pave the way for new approaches to determine cardiovascular risk and to develop personalized therapies to treat atherosclerosis and its complications.
新出现的证据表明，“非遗传因素”在动脉粥样硬化血管疾病的发病机制中变得越来越重要。事实上，遗传基因组仅决定了风险概况的一部分，因为基因组方法没有考虑到“表观遗传”变化对生物调节的额外层次。表观遗传修饰被定义为 DNA/组蛋白复合物的可塑化学变化，这些变化会严重影响基因活性，而不会改变 DNA 序列。这些修饰包括 DNA 甲基化、组蛋白翻译后修饰以及非编码 RNA，并且具有在转录和转录后水平调节基因表达的能力。值得注意的是，表观遗传信号主要由环境因素（如污染、吸烟、噪音）诱导，一旦获得，就可能传递给后代。不利的表观遗传变化的遗传可能导致涉及血管损伤和内皮功能障碍的途径过早失调。在这里，我们描述了表观遗传修饰作为动脉粥样硬化中基因转录的微调因子的新作用。具体而言，详细描述了以下几个方面：（1）表观基因组在心血管疾病中的发现和影响，（2）动脉粥样硬化中的表观遗传景观；（3）表观遗传信号的遗传和过早的血管疾病；（4）脂质代谢、血管氧化应激、炎症、自噬和细胞凋亡的表观遗传调控；（5）动脉粥样硬化患者的表观遗传生物标志物；（6）调节表观遗传标记的新治疗策略。了解个体的表观遗传谱可能为确定心血管风险和开发治疗动脉粥样硬化及其并发症的个体化治疗方法开辟新途径。
