Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital, Institute of Translational Medicine, Zhejiang University, 268 Kaixuan Road, Hangzhou, China.
Semin Cell Dev Biol. 2021 Oct;118:150-162. doi: 10.1016/j.semcdb.2021.07.007. Epub 2021 Jul 17.
In the past two decades, thousands of non-coding RNAs (ncRNAs) have been discovered, annotated, and characterized in nearly every tissue under both physiological and pathological conditions. Here, we will focus on the role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in ischemic heart disease (IHD), which remains the leading cause of morbidity and mortality in humans-resulting in 8.9 million deaths annually. Cardiomyocyte (CM) proliferation, differentiation, and survival in addition to neovascularization of injured tissues and the prevention of fibrosis are commonly regarded as critically important for the recovery of the heart following myocardial infarction (MI). An abundance of evidence has been accumulated to show ncRNAs participate in cardiac recovery after MI. Because miRNAs are important regulators of cardiac regeneration, the therapeutic potential of at least five of these molecules has been assessed in large animal models of human IHD. In particular, miRNA-based interventions based on miR-132 and miR-92a inhibition in related diseases have displayed favorable outcomes that have provided the impetus for miRNA-based clinical trials for IHD. At the same time, the functional roles of lncRNAs and circRNAs in cardiac regeneration are also being explored. In the present review, we will summarize the latest ncRNA studies aimed at reversing damage to the ischemic heart and discuss the therapeutic potential of targeting miRNAs, lncRNAs, and circRNAs to stimulate cardiac regeneration.
在过去的二十年中，在生理和病理条件下，几乎在所有组织中都发现、注释和表征了数千种非编码 RNA（ncRNA）。在这里，我们将重点介绍 ncRNA，包括 microRNAs（miRNAs）、长非编码 RNA（lncRNA）和环状 RNA（circRNA）在缺血性心脏病（IHD）中的作用，IHD 仍然是人类发病率和死亡率的主要原因-每年导致 890 万人死亡。心肌细胞（CM）的增殖、分化和存活以及受伤组织的新生血管形成和纤维化的预防通常被认为对心肌梗死后心脏的恢复至关重要。大量证据表明，ncRNA 参与了心肌梗死后的心脏恢复。由于 miRNA 是心脏再生的重要调节剂，至少有五种这些分子的治疗潜力已在人类 IHD 的大型动物模型中进行了评估。特别是，基于 miR-132 和 miR-92a 抑制的 miRNA 干预在相关疾病中显示出良好的结果，为 IHD 的 miRNA 临床试验提供了动力。同时，lncRNA 和 circRNA 在心脏再生中的功能作用也在探索中。在本综述中，我们将总结旨在逆转缺血性心脏损伤的最新 ncRNA 研究，并讨论靶向 miRNA、lncRNA 和 circRNA 以刺激心脏再生的治疗潜力。
