Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute Myocardial Infarction Patients

Zhang, Ping; Shao, Liang; Ma, Jun

doi:10.1536/ihj.17-084

Cited by 30 publications

(25 citation statements)

References 31 publications

(32 reference statements)

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“…Among the identified hub genes, CXCR2, TLR4 and CXCR4 were the top 3 genes. Recent studies have demonstrated that CXCR2 has been implicated in the pathogenesis of Ang-II-induced cardiac remodeling [24,25]. Atrial remodeling, such as atrial fibrosis, contributes to the pathogenesis of atrial fibrillation.…”

Section: Discussionmentioning

confidence: 99%

“…Atrial remodeling, such as atrial fibrosis, contributes to the pathogenesis of atrial fibrillation. TLR4 has been reported to be related to new-onset atrial fibrillation in acute myocardial infarction [25]. Soppert's study has shown that CXCR4 is involved in myofibroblast necroptosis, which may modulate cardiac remodeling in heart failure [26].…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation

2020

Preprint

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a These two authors contributed equally to this work Abstract Background： Atrial fibrillation (AF) is the most prevalent tachycardia. The major injuries caused by AF are systemic embolism and heart failure. Although AF therapies have evolved substantially in recent years, the success rate of sinus rhythm maintenance is relatively low. The reason is the incomplete understanding of the AF mechanisms. Material and method:In this study, profiles were downloaded from the GEO database (GSE79762).Bioinformatic analysis was used to identify differentially expressed genes (DEGs).GO analysis and KEGG analysis were performed to identify the most enriched terms and pathways. A protein-protein interaction network was constructed to determine regulatory genes. Key modules and hub genes were identified by MOCDE and cytoHubba. Transcription factors (TFs) were predicted by PASTAA. Results:Seventy-seven up-regulated DEGs and 236 downregulated DEGs were identified. In the GO biological process, cellular components, and molecular function analysis, positive regulation of cell migration, anchoring junction and cell adhesion molecule binding were the most significant enrichment terms. The Hippo signaling pathway was the most significantly enriched pathway. In the PPI network analysis, we found that Class A/1 (rhodopsin-like receptors) may be the critical module in AF. Ten hub genes were extracted, including 4 upregulated genes and 6 downregulated genes.CXCR2, TLR4 and CXCR4 may play critical roles in AF. In TF prediction, we found that Irf-1 may be implicated in AF. Conclusion:Our study found that the CXCR4, TLR4, CXCR2; Hippo signaling pathway; and class A/1 (rhodopsin-like receptors) modules may play critical roles in AF occurrence and maintenance. This may provide novel targets for AF treatment. , and Treatment. Mayo Clin Proc, 2016. 91(12): p. 1778-1810. Prevention 4.Dobrev, D. and S. Nattel, New antiarrhythmic drugs for treatment of atrial fibrillation. Lancet, 2010. 375(9721): p. 1212-23. 5.Dobrev, D., L. Carlsson, and S. Nattel, Novel molecular targets for atrial fibrillation therapy. Nat Rev Drug Discov, 2012. 11(4): p. 275-91. 6.Heijman, J., N. Voigt, and D. Dobrev, New directions in antiarrhythmic drug therapy for atrial fibrillation. Future Cardiol, 2013. 9(1): p. 71-88.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation

2020

Preprint

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“…Except for sympathetic nerve remodeling, cardiac structure remodeling also plays a critical role in the occur-rence of arrhythmias after MI, 33) especially beyond the subacute period after MI. 4) Myocardial remodeling, characterized by death of normal myocardial cells and formation of fibrosis and scar tissue, is the response to variable environment stimuli including myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Angiotensin Receptor Neprilysin Inhibitors on Inducibility of Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

et al. 2019

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The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis. (Int Heart J 2019; 60: 1168-1175

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“…From that perspective, the present findings are promising for discerning the risk of AF in the setting of AMI at an early phase. In this article, the expression of TLR2 and TLR4 in PBMCs of AMI patients had an association with AF onset, 14) but it is uncertain whether PBMCs expressing high levels of TLR2 and TLR4 themselves are initiators of AF, and whether high TLR2 and TLR4 PBMCs are the same population as low TLR2 and TLR4 cells. In any event, further studies will be needed to develop a novel strategy against AF in the setting of AMI, and anti-inflammatory therapy to inhibit AF will be one of the candidates for improving the mortality of AMI and suppressing its burden.…”

Section: Cd16mentioning

confidence: 97%

“…14) They collected blood samples before any reperfusion therapy within two hours after AMI onset, and divided the clinical subjects into two groups: patients with new-onset AF in 1 month after AMI (AFMI group) or without (MI group). The results showed that the expressions of both TLR2 and TLR4 in PBMCs in the MI group were higher than that in healthy volunteers, and much higher in PBMCs in the AFMI group.…”

Section: Article P64mentioning

confidence: 99%

Can Anti-inflammatory Therapy Prevent Atrial Fibrillation in Myocardial Infarction Patients?

Nakayama

Fujiu

2018

Int. Heart J.

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C ardiovascular diseases still remain one of the greatest health challenges. While the incidence and case-fatality rate of acute myocardial infarction (AMI) have decreased with the development of medications and reperfusion therapy, the disease burden of complications has increased. 1) Arrhythmia in the setting of AMI is an adverse prognostic factor, and atrial fibrillation (AF), the most frequent supraventricular arrhythmia, is associated with the increased risk of short-term and longterm mortality.2,3) In addition, AMI patients with AF have more comorbidities as compared to patients in sinus rhythm, which relate to a higher re-infarction rate, higher stroke rate, and higher risk for heart failure. [4][5][6] The presence of AF requires anti-coagulant therapy for the prevention of strokes, although anticoagulant drug administration plus dual anti-platelet therapy after percutaneous coronary intervention would increase the risk of bleeding and a variety of clinical trials have been conducted to evaluate alternative regimens. 7,8) Hence, the prediction and prevention of atrial fibrillation as a complication of AMI could be a meaningful strategy. In patients with left ventricular dysfunction secondary to AMI, treatment with an angiotensinconverting-enzyme (ACE) inhibitor could reduce the incidence of AF in the chronic phase. 9) Carvedilol has been shown to suppress AF and atrial flutter in a similar patient population, according to a sub-analysis in the the CAPRI-CORN study.10) Additionally, atorvastatin significantly reduced the incidence of postoperative AF after elective cardiac surgery.11,12) However, there is limited evidence suggesting that upstream medical therapy reduces the incidence of AF as primary endpoint.13) It is deemed desirable to provide preventive therapy tailored to risk stratification with respect to new-onset AF associated with AMI. Article p.64Zhang, et al. investigated the expression of Toll like receptors (TLRs) on the surface of peripheral blood mononuclear cells (PBMCs) in AMI patients. 14) They collected blood samples before any reperfusion therapy within two hours after AMI onset, and divided the clinical subjects into two groups: patients with new-onset AF in 1 month after AMI (AFMI group) or without (MI group). The results showed that the expressions of both TLR2 and TLR4 in PBMCs in the MI group were higher than that in healthy volunteers, and much higher in PBMCs in the AFMI group. Protein assay and flow cytometry analysis also showed a significant difference in TLR2 and TLR4 expression. With respect to the TLR adaptor proteins, myeloid differentiation factor 88 (MyD88) and TIR domain-containing protein-β antibody (TRIF-β), their protein levels were significantly higher in the AFMI group than in the MI group as well, indicating that the TLR2 and TLR4 pathway was surely augmented in PBMCs in the AFMI group. Of note, these differences were already found in the very rapid phase of AMI onset.Evidence to support the involvement of the inflammatory process in the pathophysiology of AF has...

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Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute Myocardial Infarction Patients

Cited by 30 publications

References 31 publications

Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation

Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation

Effects of Angiotensin Receptor Neprilysin Inhibitors on Inducibility of Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Can Anti-inflammatory Therapy Prevent Atrial Fibrillation in Myocardial Infarction Patients?

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