IRCCS Neuromed, Pozzilli, Isernia, Italy.
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Cell Mol Life Sci. 2020 Dec;77(24):5121-5130. doi: 10.1007/s00018-020-03573-0. Epub 2020 Jun 18.
The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to preserve regular functions and health. The concentration level of each component of the family is of crucial importance to guarantee a proper control of both systemic and local cardiovascular functions. A fine equilibrium between gene expression, protein secretion and clearance is needed to achieve the final optimal level of NPs. To this aim, the regulation of gene expression and translation plays a key role. In this regard, we know the existence of fine regulatory mechanisms, the so-called epigenetic mechanisms, which target many genes at either the promoter or the 3'UTR region to inhibit or activate their expression. The gene encoding ANP (NPPA) is regulated by histone modifications, DNA methylation, distinct microRNAs and a natural antisense transcript (NPPA-AS1) with consequent implications for both health and disease conditions. Notably, ANP modulates microRNAs on its own. Histone modifications of BNP gene (NPPB) are associated with several cardiomyopathies. The proBNP processing is regulated by miR30-GALNT1/2 axis. Among other components of the NPs family, CORIN, NPRA, NPRC and NEP may undergo epigenetic regulation. A better understanding of the epigenetic control of the NPs family will allow to gain more insights on the pathological basis of common cardiovascular diseases and to identify novel therapeutic targets. The present review article aims to discuss the major achievements obtained so far with studies on the epigenetic modulation of the NPs family.
利钠肽（NPs）家族，包括一类激素及其受体，在心血管系统中因其对维持正常功能和健康的有益作用而广为人知。家族中每个成分的浓度水平对保证全身和局部心血管功能的适当控制至关重要。需要在基因表达、蛋白质分泌和清除之间达到精细的平衡，以达到 NPs 的最终最佳水平。为此，基因表达和翻译的调控起着关键作用。在这方面，我们知道存在精细的调节机制，即所谓的表观遗传机制，这些机制靶向启动子或 3'UTR 区域的许多基因，以抑制或激活其表达。ANP（NPPA）的编码基因受组蛋白修饰、DNA 甲基化、不同的 microRNAs 和天然反义转录本（NPPA-AS1）的调控，对健康和疾病状况都有影响。值得注意的是，ANP 可以自身调节 microRNAs。BNP 基因（NPPB）的组蛋白修饰与几种心肌病有关。proBNP 的加工受 miR30-GALNT1/2 轴的调节。NPs 家族的其他成分，如 CORIN、NPRA、NPRC 和 NEP，可能也受到表观遗传调控。更好地了解 NPs 家族的表观遗传调控将有助于深入了解常见心血管疾病的病理基础，并确定新的治疗靶点。本文综述了迄今为止在 NPs 家族的表观遗传调控研究方面取得的主要成果。
