Abstract
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs. In this review, we first summarize the broad aspects of lncRNAs in various heart disease settings, then focus on their potential roles in AF development and pathophysiology. We also discuss current uses of PSCs in AF research and describe how these studies could be developed into novel therapeutics for AF and other cardiovascular diseases.
Highlights
Atrial fibrillation (AF) is the most common form of cardiac arrhythmias among heart patients [1], which leads to heart failure and other complications, which increase morbidity and mortality [2]
They postulated that the Long non-coding RNAs (lncRNAs) identified in their study were responsible for AF initiation by promoting electrical remodeling and altering the renin-angiotensin system (RAS)
Another study that examined lncRNAs associated with immune signaling, identified co-expression networks between up-regulated messenger RNAs (mRNAs) and lncRNAs in lymphocytes collected from AF and non-AF patients [142]
Summary
Atrial fibrillation (AF) is the most common form of cardiac arrhythmias among heart patients [1], which leads to heart failure and other complications, which increase morbidity and mortality [2]. With the advancement of new RNA sequencing technologies, a large set of noncoding RNAs (ncRNAs) were characterized in AF patients, which were believed to have essential roles in both atrial development and disease [9]. MicroRNAs (miRNAs), a subgroup of short non-coding RNAs, have been widely studied in AF and shown to play an essential role in this condition [10,11]. The identification and characterization of new lncRNAs could shed light on the mechanisms behind AF and may serve to prevent, diagnose, and, treat AF. Because the causes of AF are highly variable between human and animal models, it is essential to develop appropriate disease models using human cells or tissues [15]. We discuss the studies that outline the role of lncRNAs in heart diseases such as AF, present disease-modeling approaches for AF, and discuss the experimental and conceptual challenges associated with these studies with an emphasis on improving disease modeling
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