Epigenetic regulation in myocardial infarction: Non-coding RNAs and exosomal non-coding RNAs

Abstract

Myocardial infarction (MI) is one of the leading causes of deaths globally. The early diagnosis of MI lowers the rate of subsequent complications and maximizes the benefits of cardiovascular interventions. Many efforts have been made to explore new therapeutic targets for MI, and the therapeutic potential of non-coding RNAs (ncRNAs) is one good example. NcRNAs are a group of RNAs with many different subgroups, but they are not translated into proteins. MicroRNAs (miRNAs) are the most studied type of ncRNAs, and have been found to regulate several pathological processes in MI, including cardiomyocyte inflammation, apoptosis, angiogenesis, and fibrosis. These processes can also be modulated by circular RNAs and long ncRNAs via different mechanisms. However, the regulatory role of ncRNAs and their underlying mechanisms in MI are underexplored. Exosomes play a crucial role in communication between cells, and can affect both homeostasis and disease conditions. Exosomal ncRNAs have been shown to affect many biological functions. Tissue-specific changes in exosomal ncRNAs contribute to aging, tissue dysfunction, and human diseases. Here we provide a comprehensive review of recent findings on epigenetic changes in cardiovascular diseases as well as the role of ncRNAs and exosomal ncRNAs in MI, focusing on their function, diagnostic and prognostic significance.

Keywords: circular RNAs; exosome; long non-coding RNAs; microRNAs; myocardial infarction; non-coding RNAs.

Figure 1

Role of microRNAs in MI. Some miRNAs are known to be implicated in cardiac muscle angiogenesis (A), cardiac cell survival, and proliferation (B,C). Angiogenesis is pivotal for the delivery of oxygen and essential nutrients to heart muscle. Angiogenesis can be activated or repressed by a number of microRNAs. For instance, miR-15, miR-24, miR-26, and miR-92a all repress angiogenesis through inhibition of endothelial-cell functions. In contrast, miR-210 prompts angiogenesis via inhibiting several antiangiogenic factors (A). A number of miRNAs have been identified to be involved in the apoptosis and survival of cardiac cells. Apoptosis inhibition or an increase in survival signals promotes cardiac regeneration. The miR-15 family (miR-320, miR-34, and miR-140) can serve as pro-apoptotic factors, while miR-24 and miR-214 can act as anti-apoptotic factors (B). The proliferation of cardiac cells is limited; however, cardiac regeneration can increase following stimulation of proliferation. It has been shown that miR-19, miR-199a and miR-590, can promote proliferation of cardiac cells, while both miR-15 and miR-133 inhibit cardiac cell proliferation (C). This figure adapted from Boon and Dimmeler (76).