Role of Tumor Necrosis Factor-α in the Pathogenesis of Atrial Fibrosis and Development of an Arrhythmogenic Substrate

Liew, Reginald; Khairunnisa, Katwadi; Gu, Yacui; Tee, Nicole; Yin, New Oo; Naylynn, Tin Maung; Moe, Kyaw Thu

doi:10.1253/circj.cj-12-1155

Cited by 95 publications

(66 citation statements)

References 36 publications

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“…24 Zhao et al revealed that by improving mitochondrial function in an animal model, tamoxifen protected against cardiac-injuring tumor necrosis factor α, 25 which was a novel potential therapeutic target for atrial fibrosis. 26 In another subcellular study, tamoxifen was found to induce manganese superoxide dismutase, a mitochondrial antioxidant enzyme, which protected mouse cardiomyocytes from adriamycin injury. 27 The strength of the present study was the database that spans the entire population nationwide and could trace nearly all breast cancer cases in Taiwan over the study period.…”

Section: Resultsmentioning

confidence: 97%

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Yang

Huang

et al. 2014

Circ J

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Section: Resultsmentioning

confidence: 97%

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Yang

Huang

et al. 2014

Circ J

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“…Previous studies suggested that these inflammatory cytokines play a key stimulatory role in atrial remodeling through several mechanisms. TNF‐α has been demonstrated to induce atrial fibrosis by increasing atrial myofibroblast proliferation and metalloproteinase secretion 23, 24. Saba et al25 found that cardiac‐specific overexpression of TNF‐α could cause atrial contractile dysfunction, fibrosis, and arrhythmias in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis

Dai

Wang

Yin

et al. 2017

JAHA

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BackgroundThe prevalence of atrial fibrillation (AF) is significantly higher in rheumatoid arthritis (RA) patients, but the underlying mechanisms remain poorly understood. The goal of this study was to assess the effects of RA on AF susceptibility and atrial arrhythmogenic remodeling in a rat model of RA.Methods and ResultsCollagen‐induced arthritis was induced in rats by immunization with type II collagen in Freund's incomplete adjuvant. Among the rats that developed arthritis, AF susceptibility and atrial remodeling were examined 8 weeks after the primary immunization. AF inducibility and duration were substantially increased in collagen‐induced arthritis rats, and AF duration was significantly and positively correlated with the serum IL‐6 and TNF‐α levels. Rats with collagen‐induced arthritis showed prolonged atrial conduction time with no changes in the atrial effective refractory period. Atrial conduction delay was accompanied by significantly increased atrial fibrosis. In addition, atrial structural and autonomic remodeling, including left atrial dilation, apoptosis and autophagy of atrial myocytes, and atrial heterogeneous sympathetic hyperinnervation, was observed. Interestingly, we found that collagen‐induced arthritis had no significant effects on connexins, Nav1.5, and the main ion channels' protein expressions in atria.ConclusionsWe demonstrated that RA increased AF susceptibility by inducing AF‐promoting atrial remodeling. This study may provide insights into mechanisms underlying RA‐induced AF and validate a model that is suitable for further mechanistic and therapeutic exploration.

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“…Inflammation and fibrosis are interrelated and potentially share common signaling cascades; TNF- α induces atrial fibrosis via activation of TGF- β /Smad2/3 signaling. 22 TNF- α also regulates matrix metalloproteinase activity and ECM degradation. 23 NF- κ B may also regulate the expression of Na + -channel subunits that contribute to AF-associated electrical remodeling.…”

Section: Cellular and Molecular Mechanismsmentioning

confidence: 99%

Role of Inflammation in Atrial Fibrillation Pathophysiology and Management

Harada

Wagoner

Nattel

2015

Circ J

387

290

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Atrial fibrillation (AF) is the most common clinically relevant arrhythmia, but the methods available for treating AF and its complications (of which the most important is thrombogenesis), as well as for assessing AF risk and underlying pathophysiology, are largely limited. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. That evidence includes elevated serum levels of inflammatory biomarkers in AF subjects, the expression of inflammatory markers in cardiac tissues of AF patients and animal models of AF, and beneficial effects of anti-inflammatory drugs in experimental AF paradigms. Inflammation is suggested to be linked to various pathological processes, such as oxidative stress, apoptosis, and fibrosis, that promote AF substrate formation. Inflammation has also been associated with endothelial dysfunction, platelet activation, and coagulation cascade activation, leading to thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. Here, we review the evidence for a role of inflammation and inflammatory biomarkers in the risk management and treatment of AF. We also summarize the current knowledge of inflammation-dependent cellular and molecular mechanisms in AF pathophysiology and their potential as therapeutic targets.

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Role of Tumor Necrosis Factor-α in the Pathogenesis of Atrial Fibrosis and Development of an Arrhythmogenic Substrate

Cited by 95 publications

References 36 publications

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis

Role of Inflammation in Atrial Fibrillation Pathophysiology and Management

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