TY - JOUR
T1 - Dissecting the Molecular Mechanisms Driving Electropathology in Atrial Fibrillation
T2 - Deployment of RNA Sequencing and Transcriptomic Analyses
AU - Huiskes, Fabries G.
AU - Creemers, Esther E.
AU - Brundel, Bianca J. J. M.
N1 - Funding Information: The research is funded by the Dutch Heart Foundation (2020-2020B003, DnAFix) and NWA-ORC project CIRCULAR NWO (NWA.1389.20.157). Publisher Copyright: © 2023 by the authors.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - Despite many efforts to treat atrial fibrillation (AF), the most common progressive and age-related cardiac tachyarrhythmia in the Western world, the efficacy is still suboptimal. A plausible reason for this is that current treatments are not directed at underlying molecular root causes that drive electrical conduction disorders and AF (i.e., electropathology). Insights into AF-induced transcriptomic alterations may aid in a deeper understanding of electropathology. Specifically, RNA sequencing (RNA-seq) facilitates transcriptomic analyses and discovery of differences in gene expression profiles between patient groups. In the last decade, various RNA-seq studies have been conducted in atrial tissue samples of patients with AF versus controls in sinus rhythm. Identified differentially expressed molecular pathways so far include pathways related to mechanotransduction, ECM remodeling, ion channel signaling, and structural tissue organization through developmental and inflammatory signaling pathways. In this review, we provide an overview of the available human AF RNA-seq studies and highlight the molecular pathways identified. Additionally, a comparison is made between human RNA-seq findings with findings from experimental AF model systems and we discuss contrasting findings. Finally, we elaborate on new exciting RNA-seq approaches, including single-nucleotide variants, spatial transcriptomics and profiling of different populations of total RNA, small RNA and long non-coding RNA.
AB - Despite many efforts to treat atrial fibrillation (AF), the most common progressive and age-related cardiac tachyarrhythmia in the Western world, the efficacy is still suboptimal. A plausible reason for this is that current treatments are not directed at underlying molecular root causes that drive electrical conduction disorders and AF (i.e., electropathology). Insights into AF-induced transcriptomic alterations may aid in a deeper understanding of electropathology. Specifically, RNA sequencing (RNA-seq) facilitates transcriptomic analyses and discovery of differences in gene expression profiles between patient groups. In the last decade, various RNA-seq studies have been conducted in atrial tissue samples of patients with AF versus controls in sinus rhythm. Identified differentially expressed molecular pathways so far include pathways related to mechanotransduction, ECM remodeling, ion channel signaling, and structural tissue organization through developmental and inflammatory signaling pathways. In this review, we provide an overview of the available human AF RNA-seq studies and highlight the molecular pathways identified. Additionally, a comparison is made between human RNA-seq findings with findings from experimental AF model systems and we discuss contrasting findings. Finally, we elaborate on new exciting RNA-seq approaches, including single-nucleotide variants, spatial transcriptomics and profiling of different populations of total RNA, small RNA and long non-coding RNA.
KW - RNA sequencing
KW - atrial fibrillation
KW - pathophysiology
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85172773984&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cells12182242
DO - https://doi.org/10.3390/cells12182242
M3 - Review article
C2 - 37759465
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 18
M1 - 2242
ER -