Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion

Raman, Kripa; Aeschbacher, Stefanie; Bossard, Matthias; Hochgruber, Thomas; Zimmermann, Andreas; Kaufmann, Beat A.; Pumpol, Katrin; Rickenbacker, Peter; Paré, Guillaume; Conen, David

doi:10.1371/journal.pone.0157550

Cited by 14 publications

(9 citation statements)

References 30 publications

(30 reference statements)

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“…However, Lin et al (31) studied the association of whole blood gene expression with AF in a large community-based cohort, and identified 7 genes markedly upregulated with prevalent AF. Raman et al (32) also elucidated peripheral blood gene expression in patients with persistent AF that underwent electrical cardioversion. In another study, peripheral monocyte toll-like receptor (TLR) expression levels have been investigated and elevated TLR-2 and TLR-4 expressions were detected in patients with AF (33).…”

Section: Discussionmentioning

confidence: 99%

Investigation of leukocyte RHO/ROCK gene expressions in patients with non‑valvular atrial fibrillation

et al. 2019

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Atrial fibrillation (AF) is an arrhythmia caused by disorganized electrical activity in the atria, and it is an important cause of mortality and morbidity. There is a limited data about Rho/Rho-kinase (ROCK) pathway contribute to AF development. The aim of the present study was to elucidate leukocyte RHO/ROCK gene expressions in patients with non-valvular AF (NVAF). A total of 37 NVAF patients and 47 age and sex-matched controls were included in this study. mRNA was extracted from leukocytes, and real-time polymerase chain reaction was used for gene expression analysis. A marked increase in ROCK1 and ROCK2 gene expressions in patients with NVAF was observed (P<0.0001). The present study detected significant elevations in RHOBTB2, RND3 (RHOE), RHOC, RHOG, RHOH, RAC3, RHOB, RHOD, RHOV, RHOBTB1, RND2, RND1 and RHOJ gene expressions (P<0.01). However, there were marked decreases in CDC42, RAC2, and RHOQ gene expressions in patients with NVAF. No significant modifications were seen in the other Rho GTPase proteins RHOA, RAC1, RHOF, RHOU and RHOBTB3. To the best of our knowledge, the present study is the first to provide data that gene expression of leukocyte RHO/ROCK may contribute to the NVAF pathogenesis through activated leukocytes, which promotes the immune or inflammatory cascade.

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Section: Discussionmentioning

confidence: 99%

Investigation of leukocyte RHO/ROCK gene expressions in patients with non‑valvular atrial fibrillation

et al. 2019

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“…Raman et al . 55 also evaluated peripheral blood gene expression in patients with persistent AF that underwent electrical cardioversion. In a recent study, peripheral monocyte toll-like receptor (TLR) expression levels have been investigated and higher levels of TLR-2 and TLR-4 expressions were detected in patients with AF 56 .…”

Section: Discussionmentioning

confidence: 99%

Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation

Düzen

Yavuz

Vuruşkan

et al. 2017

Sci Rep

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Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls. mRNA was extracted from blood samples, and real-time polymerase chain reaction was performed for gene expressions by using a dynamic array system. Low levels of TRP channel expressions in the controls were markedly potentiated in NVAF group. We observed marked increases in MCOLN1 (TRPML1), MCOLN2 (TRPML2), MCOLN3 (TRPML3), TRPA1, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6, and PKD2 (TRPP2) gene expressions in NVAF patients (P < 0.05). However, there was no change in PKD1 (TRPP1) gene expression. This is the first study to provide evidence that elevated gene expressions of TRP channels are associated with the pathogenesis of NVAF.

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“…In the absence of heart failure, it has been demonstrated that NT-proBNP is released primarily by the atria because of the increased myocardial contraction, volume load and wall stress caused by AF 19 . In previous studies including an analysis from this dataset, restoration of sinus rhythm through cardioversion led to a decrease in natriuretic peptides concentrations [20][21][22] . Our data extend these previous reports by demonstrating within-person reductions in NT-proBNP during a short-term follow-up in patients who were in sinus rhythm, and persistently elevated levels in those who remained in AF.…”

Section: Discussionmentioning

confidence: 75%

Biomarker Levels in Patients with Atrial Fibrillation Before and After Electrical Cardioversion

Meyre

Aeschbacher

Blum

et al. 2021

Preprint

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Background Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. We aimed to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. Methods Patients with persistent AF undergoing elective electrical cardioversion were enrolled. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up using multivariable logistic regression models. Results Of the 100 patients included (mean [SD] age 66 (10) years, 25% women), 28 (28%) had an AF recurrence. Of the 21 biomarkers assessed, 4 reached the predefined between group significance of p<0.01. The most significant ones were bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were -10.4%, -62.0% and -25.6% in patients with sinus rhythm, and 3.1%, 1.1% and -9.4% in patients with recurrent AF, for a between group difference of -13.5% (95% confidence interval [CI], -19.3% to -7.6%; P<0.001), -63.1% (95% CI, -76.6% to -49.6%; P<0.001) and -16.3 (95% CI, -27.9% to -4.7%; P=0.007). In age and sex adjusted models, reductions of BMP10 and NT-proBNP were significantly associated with rhythm status at follow-up (β coefficient per 1-SD decrease, -2.03; 95% CI, -3.06 to -1.00; P<0.001 and -3.98; 95% CI, -5.75 to -2.22; P<0.001, respectively). After additional adjustment for demographic characteristics, risk factors for AF, and changes in clinical measures, the β coefficients per 1-SD were -3.85 (95% CI, -6.34 to -1.35; P=0.003) for BMP10 and -5.84 (95% CI, -10.22 to -1.47; P=0.009) for NT-proBNP. Conclusions Changes in BMP10 und NT-proBNP levels were strongly associated with rhythm status after electrical cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

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Whole Blood Gene Expression Differentiates between Atrial Fibrillation and Sinus Rhythm after Cardioversion

Cited by 14 publications

References 30 publications

Investigation of leukocyte RHO/ROCK gene expressions in patients with non‑valvular atrial fibrillation

Investigation of leukocyte RHO/ROCK gene expressions in patients with non‑valvular atrial fibrillation

Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation

Biomarker Levels in Patients with Atrial Fibrillation Before and After Electrical Cardioversion

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