Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System

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.

Integrated Analysis of the microRNA–mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Humans

“…As both the miR-302 family and SDC-1 have conserved sequences and function between humans and mice, mouse models may help elucidate molecular mechanisms of the miR-302b-3p/SDC-1 axis in the AF pathogenesis. Indeed, disease models with iPSC-derived fibroblasts [ 73 ] or CMs [ 74 ], which are physiologically more similar to native human cells, also offer a reliable platform for investigation of AF mechanisms as the tissue resources from patients are limited for extensive mechanistic research [ 74 , 75 ]. Experimental validations of miR-302b-3p/SDC-1 function and mechanism may help generate therapeutic approaches targeting this axis in the treatment of AF patients.…”

Integrated Analysis of microRNA-mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Human

“…As both miR-302 family and SDC-1 have conserved sequences and function between human and mouse, mouse models may help elucidate molecular mechanisms of miR-302b-3p/SDC-1 axis in AF pathogenesis. Indeed, disease models with iPSC-derived fibroblasts [72] or CMs [73], which are physiologically more similar to native human cells, also offer reliable platform for investigation of AF mechanisms as the tissue resources from patients is limited for extensive mechanistic research [73,74]. Experimental validations of miR-302b-3p/SDC-1 function and mechanism may help generate therapeutic approaches targeting this axis toward the treatment of AF patients.…”

Role of long non‐coding RNAs in adipogenesis: State of the art and implications in obesity and obesity‐associated diseases

“…Lastly, a study in atria from AF rabbit highlighted 99,843 putative new lncRNAs, of which TCONS_00075467 was selected to be important for electrical remodeling, possibly through sponging of miR‐328 and subsequent regulation of CACNA1C 141 . Other lncRNAs implicated in AF include TCONS_00202959, 142 AK055347, 143 MIAT, 110 KCNQ1OT1, 144 and others extensively reviewed in previous publications 135,145–147 . When focusing on the adipose tissue implication in AF, the number of studies is more restricted, but a very recent work performed a RNA‐sequencing analysis in epicardial adipose tissue samples of patients with persistent non‐valvular AF and sinus rhythm, highlighting 57 differentially expressed lncRNAs 148 …”