Background:The discovery that much of the non–protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion in the development of tools and technologies to investigate the role of these noncoding RNAs in cardiovascular health. Furthermore, identifying noncoding RNAs for targeted therapeutics to treat cardiovascular disease is an emerging area of research. The purpose of this statement is to review existing literature, offer guidance on tools and technologies currently available to study noncoding RNAs, and identify areas of unmet need.Methods:The writing group used systematic literature reviews (including MEDLINE, Web of Science through 2018), expert opinion/statements, analyses of databases and computational tools/algorithms, and review of current clinical trials to provide a broad consensus on the current state of the art in noncoding RNA in cardiovascular disease.Results:Significant progress has been made since the initial studies focusing on the role of miRNAs (microRNAs) in cardiovascular development and disease. Notably, recent progress on understanding the role of novel types of noncoding small RNAs such as snoRNAs (small nucleolar RNAs), tRNA (transfer RNA) fragments, and Y-RNAs in cellular processes has revealed a noncanonical function for many of these molecules. Similarly, the identification of long noncoding RNAs that appear to play an important role in cardiovascular disease processes, coupled with the development of tools to characterize their interacting partners, has led to significant mechanistic insight. Finally, recent work has characterized the unique role of extracellular RNAs in mediating intercellular communication and their potential role as biomarkers.Conclusions:The rapid expansion of tools and pipelines for isolating, measuring, and annotating these entities suggests that caution in interpreting results is warranted until these methodologies are rigorously validated. Most investigators have focused on investigating the functional role of single RNA entities, but studies suggest complex interaction between different RNA molecules. The use of network approaches and advanced computational tools to understand the interaction of different noncoding RNA species to mediate a particular phenotype may be required to fully comprehend the function of noncoding RNAs in mediating disease phenotypes.

中文翻译：

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心血管疾病中的非编码 RNA：当前知识、研究工具和技术以及未来方向：美国心脏协会的科学声明。

背景：许多非蛋白质编码基因组被转录并在基本细胞过程中发挥多种功能作用的发现导致了研究这些非编码 RNA 在心血管健康中的作用的工具和技术的发展。此外，为心血管疾病的靶向治疗鉴定非编码 RNA 是一个新兴的研究领域。本声明的目的是回顾现有文献，为目前可用于研究非编码 RNA 的工具和技术提供指导，并确定未满足需求的领域。方法：写作小组使用系统文献回顾（包括 MEDLINE、Web of Science 到 2018 年） ，专家意见/陈述，数据库分析和计算工具/算法，并回顾当前的临床试验，以就心血管疾病中非编码 RNA 的现有技术水平达成广泛共识。 结果：自最初关注 miRNA (microRNA) 在心血管发育和疾病中的作用的研究以来，已经取得了重大进展. 值得注意的是，最近在理解新型非编码小 RNA（如 snoRNA（小核仁 RNA）、tRNA（转移 RNA）片段和 Y-RNA）在细胞过程中的作用方面取得的进展揭示了其中许多分子的非规范功能。同样，鉴定似乎在心血管疾病过程中发挥重要作用的长链非编码 RNA，以及开发用于表征其相互作用伙伴的工具，已经导致了重要的机制洞察力。最后，最近的工作已经描述了细胞外 RNA 在介导细胞间通讯中的独特作用及其作为生物标志物的潜在作用。结论：用于分离、测量和注释这些实体的工具和管道的快速扩展表明，在这些方法之前解释结果时要谨慎都经过严格验证。大多数研究人员专注于研究单个 RNA 实体的功能作用，但研究表明不同 RNA 分子之间存在复杂的相互作用。可能需要使用网络方法和先进的计算工具来了解不同非编码 RNA 种类介导特定表型的相互作用，以充分理解非编码 RNA 在介导疾病表型中的功能。