atrial fibrosis
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2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Liao ◽  
Shaoshao Zhang ◽  
Shuaitao Yang ◽  
Yang Lu ◽  
Kai Lu ◽  
...  

Pre-existing Ca2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 μg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo. IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.


2021 ◽  
Vol 10 (4) ◽  
pp. 225-229
Author(s):  
Christian Mahnkopf ◽  
Younghoon Kwon ◽  
Nazem Akoum

Atrial fibrosis is an important component of the arrhythmic substrate in AF. Evidence suggests that atrial fibrosis also plays a role in increasing the risk of stroke in patients with the arrhythmia. Patients with embolic stroke of undetermined source (ESUS), who are suspected to have AF but are rarely shown to have it, frequently demonstrate evidence of atrial fibrosis; measured using late-gadolinium enhancement MRI, this manifests as atrial remodelling encompassing structural, functional and electrical properties. In this review, the authors discuss the available evidence linking atrial disease, including fibrosis, with the risk of ischaemic stroke in AF, as well as in the ESUS population, in whom it has been linked to recurrent stroke and new-onset AF. They also discuss the implications of this association on future research that may elucidate the mechanism of stroke and stroke prevention strategies in the AF and ESUS populations.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1900
Author(s):  
Cheng-Chih Chung ◽  
Chye-Gen Chin ◽  
Yung-Kuo Lin ◽  
Yao-Chang Chen ◽  
Wan-Li Cheng ◽  
...  

Atrial fibrosis plays a key role in atrial myopathy, resulting in the genesis of atrial fibrillation (AF). The abnormal distribution of fibrotic tissue, electrical coupling, paracrine interactions, and biomechanical–electrical interactions have all been suggested as causes of fibrosis-related arrhythmogenesis. Moreover, the regional difference in fibrogenesis, specifically the left atrium (LA) exhibiting a higher arrhythmogenesis and level of fibrosis than the right atrium (RA) in AF, is a key contributor to atrial arrhythmogenesis. LA fibroblasts have greater profibrotic cellular activities than RA fibroblasts, but knowledge about the regional diversity of atrial regional fibrogenesis remains limited. This article provides a comprehensive review of research findings on the association between fibrogenesis and arrhythmogenesis from laboratory to clinical evidence and updates the current understanding of the potential mechanism underlying the difference in fibrogenesis between the LA and RA.


2021 ◽  
Author(s):  
Xue Liang ◽  
Yanhong Liu ◽  
Yu Liu ◽  
Weiding Wang ◽  
Wenfeng Shangguan ◽  
...  

Abstract Aims: This study aimed to characterize circular RNA (circRNA) profiles associated with atrial fibrosis and identify critical circRNAs in a rat model of atrial fibrosis.Methods: Sprague Dawley rats were randomly divided into control and atrial fibrosis groups (n=15 in each group). For rats in the atrial fibrosis group, atrial fibrosis was induced by chronic intermittent hypoxia. Atrial tissues were isolated for circRNA sequencing. The dysregulated circRNAs in atrial fibrosis were identified by DESeq. Subsequently, the potential functions of circRNAs in atrial fibrosis were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the host genes. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were analyzed by constructing a competing endogenous RNA (ceRNA) network. Finally, the crucial circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR).Results: Five upregulated and 11 downregulated circRNAs were identified in the atrial fibrosis group. These dysregulated circRNAs were primarily associated with “carbohydrate metabolism” and “cardiovascular diseases.” Two circRNAs (circRNA_0263 and circRNA_1507) were able to regulate target gene expression by interacting with corresponding miRNAs, including rno-miR-29b-5p, rno-miR-29b-3p, rno-miR-496-5p, rno-miR-136-5p, and novel123-mature. qRT-PCR successfully validated the differential expression of circRNA_0263 and circRNA_1507.Conclusion: A series of circRNAs were identified as dysregulated in an atrial fibrosis rat model. The dysregulation of two circRNAs (circRNA_0263 and circRNA_1507) might be crucial for atrial fibrosis development by competing with several miRNAs.


2021 ◽  
Vol 12 ◽  
Author(s):  
Heng-Jing Hu ◽  
Xiu-Heng Wang ◽  
Yao Liu ◽  
Tian-Qing Zhang ◽  
Zheng-Rong Chen ◽  
...  

Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H2S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H2S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H2S level, induce cystathionine-β-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration- and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H2S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Luuk H. G. A. Hopman ◽  
Mark J. Mulder ◽  
Anja M. van der Laan ◽  
Ahmet Demirkiran ◽  
Pranav Bhagirath ◽  
...  

Abstract Background Atrial fibrillation (AF) is associated with profound structural and functional changes in the atria. In the present study, we investigated the association between left atrial (LA) phasic function and the extent of LA fibrosis using advanced cardiovascular magnetic resonance (CMR) imaging techniques, including 3-dimensional (3D) late gadolinium enhancement (LGE) and feature tracking. Methods Patients with paroxysmal and persistent AF (n = 105) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using CMR feature tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy subjects underwent CMR and served as controls (n = 19). Results Significantly lower LA reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to healthy controls (− 15.9 ± 3.8% vs. − 21.1 ± 3.6% P < 0.001, − 8.7 ± 2.7% vs. − 12.6 ± 2.5% P < 0.001 and − 7.2 ± 2.3% vs. − 8.6 ± 2.2% P = 0.02, respectively). Patients with a high degree of LA fibrosis (dichotomized by the median value) had lower reservoir strain and conduit strain compared to patients with a low degree of LA fibrosis (− 15.0 ± 3.9% vs. − 16.9 ± 3.3%, P = 0.02 and − 7.9 ± 2.7% vs. − 9.5 ± 2.6%, P = 0.01, respectively). In contrast, no difference was found for LA contractile strain (− 7.1 ± 2.4% vs. − 7.4 ± 2.3%, P = 0.55). Conclusions Impaired LA reservoir and conduit strain are present in AF patients with extensive atrial fibrosis. Future studies are needed to examine the biologic nature of this association and possible therapeutic implications.


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