Establishment of a lncRNA-miRNA-mRNA network in a rat model of atrial fibrosis by whole transcriptome sequencing

Zhao, Bo; Wang, Weiding; Liu, Yu; Guan, Siyu; Wang, Manman; Song, Fang; Shangguan, Wenfeng; Song, Miao; Zhang, Xiaowei; Liu, Huijia; Liu, Enzhao; Li, Xue

doi:10.1007/s10840-022-01120-4

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…A large body of evidence supports the view that CIH mediates significant atrial structural remodelling, adversely affecting AF inducibility. Atrial fibrosis is a common response to CIH, and this is consistent with reports of upregulated TGF-β, CTGF, and α-smooth muscle actin [ 39 , 45 , 46 , 47 , 48 , 56 , 73 , 74 , 75 , 76 , 77 ]. These pro-fibrotic events are closely linked to the inflammatory response, with markers such as TNF-α, IL-6, and IL-1β extensively reported in both animal models and OSA patients [ 64 , 70 ].…”

Section: Arrhythmogenic Mechanisms In Osasupporting

confidence: 90%

Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

Saleeb-Mousa,

Nathanael,

Coney

et al. 2023

Cells

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Obstructive sleep apnoea (OSA) is a strong independent risk factor for atrial fibrillation (AF). Emerging clinical data cite adverse effects of OSA on AF induction, maintenance, disease severity, and responsiveness to treatment. Prevention using continuous positive airway pressure (CPAP) is effective in some groups but is limited by its poor compliance. Thus, an improved understanding of the underlying arrhythmogenic mechanisms will facilitate the development of novel therapies and/or better selection of those currently available to complement CPAP in alleviating the burden of AF in OSA. Arrhythmogenesis in OSA is a multifactorial process characterised by a combination of acute atrial stimulation on a background of chronic electrical, structural, and autonomic remodelling. Chronic intermittent hypoxia (CIH), a key feature of OSA, is associated with long-term adaptive changes in myocyte ion channel currents, sensitising the atria to episodic bursts of autonomic reflex activity. CIH is also a potent driver of inflammatory and hypoxic stress, leading to fibrosis, connexin downregulation, and conduction slowing. Atrial stretch is brought about by negative thoracic pressure (NTP) swings during apnoea, promoting further chronic structural remodelling, as well as acutely dysregulating calcium handling and electrical function. Here, we provide an up-to-date review of these topical mechanistic insights and their roles in arrhythmia.

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Section: Arrhythmogenic Mechanisms In Osasupporting

confidence: 90%

Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

Saleeb-Mousa,

Nathanael,

Coney

et al. 2023

Cells

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“…In order to preliminarily clarify the regulatory role of upstream signaling pathway in CIH-induced atrial remodeling, whole transcriptome sequencing was performed to identify crucial lncRNAs, microRNAs and mRNAs [19]. Given the crucial role of miRs in cardiovascular biology and disease [20], several miRs which related to atrial remodeling were further veri ed in our subsequent RT-qPCR assay (Figure S2).…”

Section: Discussionmentioning

confidence: 99%

Effects of doxycycline on atrial electrical remodeling in a rat model of atrial fibrillation

Zhang

et al. 2023

Preprint

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Purpose Previous studies showed that doxycycline (Dox), a matrix metalloproteinase inhibitor, can attenuate chronic intermittent hypoxia (CIH)-induced atrial fibrosis in our rats. On this basis, we further investigated the effects of Dox on CIH-induced atrial electrical remodeling in rats. Methods Rats were randomized into 3 groups: Control group, CIH group, and CIH with Dox treatment (CIH-D) group (n = 30). CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks. After collecting the basic parameters of the rats, atrial fibrillation (AF) inducibility, conduction inhomogeneity, and epicardial conduction velocity were examined by vitro cardiac electrophysiology experiments. The expression levels of ion channel subunits in atrium were detected by Western blotting. Whole-cell patch clamp experiments were used to recorded action potential (AP), INa, ICa−L, Ito, and the kinetic parameters. Results Compared to the Control rats, CIH rats showed increased AF inducibility, conduction inhomogeneity, and expression levels of p-RyR2, p-CaMKII, Kv11.1, Kir2.3, KCa3.1, while the epicardial conduction velocity, ICa−L, Ito, and expression levels of Cav1.2, Kv1.5, Kv4.3 were decreased. Dox-treatment significantly improved the expression levels of Kv1.5, Kv4.3 and Kir2.3 in CIH-D rats. Conclusion CIH caused atrial electrical remodeling in our rats, which was improved by Dox treatment. These changes indicated the potential effects of Dox in AF.

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“…The types of RNA-seq studies performed on these models are either a direct comparison between induced or simulated AF and controls, or studies on the effect of a treatment or a specific mutation. Differential gene expression studies in AF models in rats and rabbit suggest involvement of cell cycle-related processes, inflammatory signaling, phagosome and calcium signaling pathways [ 58 , 62 ]. Canine and sheep studies have captured a rich collection of potential AF-related transcripts, including pathway elements for muscle structural development, ECM structure, intercellular glutamate and SLIT/ROBO signaling, intracellular calcineurin signaling and ion channels [ 64 , 65 ].…”

Section: Transcriptomic Analyses In Experimental Af Model Systemsmentioning

confidence: 99%

Dissecting the Molecular Mechanisms Driving Electropathology in Atrial Fibrillation: Deployment of RNA Sequencing and Transcriptomic Analyses

Huiskes,

Creemers,

Brundel

2023

Cells

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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.

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Establishment of a lncRNA-miRNA-mRNA network in a rat model of atrial fibrosis by whole transcriptome sequencing

Cited by 6 publications

References 40 publications

Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

Effects of doxycycline on atrial electrical remodeling in a rat model of atrial fibrillation

Dissecting the Molecular Mechanisms Driving Electropathology in Atrial Fibrillation: Deployment of RNA Sequencing and Transcriptomic Analyses

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