MicroRNAs: Midfielders of Cardiac Health, Disease and Treatment

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a role in post-transcriptional gene regulation. It is generally accepted that their main mechanism of action is the negative regulation of gene expression, through binding to specific regions in messenger RNA (mRNA) and repressing protein translation. By interrupting protein synthesis, miRNAs can effectively turn genes off and influence many basic processes in the body, such as developmental and apoptotic behaviours of cells and cardiac organogenesis. Their importance is highlighted by inhibiting or overexpressing certain miRNAs, which will be discussed in the context of coronary artery disease, atrial fibrillation, bradycardia, and heart failure. Dysregulated levels of miRNAs in the body can exacerbate or alleviate existing disease, and their omnipresence in the body makes them reliable as quantifiable markers of disease. This review aims to provide a summary of miRNAs as biomarkers and their interactions with targets that affect cardiac health, and intersperse it with current therapeutic knowledge. It intends to succinctly inform on these topics and guide readers toward more comprehensive works if they wish to explore further through a wide-ranging citation list.

Keywords: atrial fibrillation; biomarker; bradycardia; heart disease; heart failure; ion channels; miRNA; sinoatrial node.

Figure 3

This is a diagram modified from Figure 3 in [78], depicting the various pathways of atherosclerotic lesion formation mentioned above. It also highlights some miRNAs altered in pathological processes involving endothelial cells, inflammation, and lipid metabolism within CAD. Note that some miRNAs are altered in more than one process. Arrows facing up depict upregulation while arrows facing down reflect downregulation in CAD. Three miRNAs (miR-126, -21 and -155) will be discussed in detail in the following section.

Figure 1

This is a diagram modified from Figure 1 in [8], depicting canonical miRNA biogenesis, and miRNA effects on mRNA.

Figure 2

This is a diagram modified from Figure 3 in [59] and Figure 3 in [60], depicting therapeutic approaches to inhibit or promote miRNA activity.

Figure 4

This is a diagram modified from Figure 7 in [96] and Figure 6 in [92]. It includes factors pertaining to HCN4 downregulation in bradycardia (discussed in Section 2.2.2 and Section 2.2.3), highlighting three important miRNAs that are confirmed to target the HCN4 channel [31,37,38] Arrows facing up depict upregulation of the key miRNAs while the arrow facing down reflects downregulation of HCN4 expression.