MicroRNAs in Atrial Fibrillation: from Expression Signatures to Functional Implications

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase for the forthcoming years, and associated frequent hospitalizations turn AF into a major health problem. Structural and electrical atrial remodelling underlie the substrate for AF, but the exact mechanisms driving this remodelling remain incompletely understood. Recent studies have shown that microRNAs (miRNA), short non-coding RNAs that regulate gene expression, may be involved in the pathophysiology of AF. MiRNAs have been implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could therefore provide insight into AF pathophysiology or become novel targets for therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been suggested as a new class of diagnostic and prognostic biomarkers of AF. However, the origin and function of miRNAs in tissue and plasma frequently remain unknown and studies investigating the role of miRNAs in AF vary in design and focus and even present contradicting results. Here, we provide a systematic review of the available clinical and functional studies investigating the tissue and plasma miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or novel therapeutic targets in AF.

Keywords: Atrial fibrillation; Electrical remodelling; Fibrosis; Therapy; microRNA.

Fig. 1

microRNAs expressed in plasma and tissue. This figure illustrates the number of miRNAs differentially expressed in tissue and in plasma in AF patients. Note the high number of upregulated miRNAs in tissue, whereas miRNAs in plasma more often have lower levels in AF. Furthermore, there is little overlap between tissue and plasma expression of the miRNAs that have lower or higher levels in AF (between the dotted lines). There is a substantial proportion of miRNAs that present contradicting results (miRNAs described to be both up- and downregulated in tissue or plasma)