Circulating Neuropeptide Y as a Biomarker for Neuromodulation in Atrial Fibrillation.
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ABSTRACT:
SUBMITTER: Stavrakis S
PROVIDER: S-EPMC8450521 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Circulating Neuropeptide Y as a Biomarker for Neuromodulation in Atrial Fibrillation.
Stavrakis Stavros S Morris Lynsie L Takashima Ayahiro D AD Elkholey Khaled K Van Wagoner David R DR Ajijola Olujimi A OA
JACC. Clinical electrophysiology 20201101 12
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Project description:Atrial fibrillation has a multifactorial pathophysiology influenced by cardiac autonomic innervation. Both sympathetic and parasympathetic influences are profibrillatory. Innovative therapies targeting the neurocardiac axis include catheter ablation or pharmacologic suppression of ganglionated plexi, renal sympathetic denervation, low-level vagal stimulation, and stellate ganglion blockade. To date, these therapies have variable efficacy. As our understanding of atrial fibrillation and the cardiac nervous system expands, our approach to therapeutic neuromodulation will continue evolving for the benefit of those with AF.
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Project description:BackgroundCirculating long noncoding RNA (lncRNA) plays a vital role in clinical disease diagnosis and prognosis. Here, we evaluate the role of a lncRNA, named growth arrest specific 5 (GAS5), in atrial fibrillation (AF).MethodsExpression of GAS5 was measured by qRT-PCR. Diagnostic and prognostic values of GAS5 were assessed by the receiver operating characteristics curve (ROC), Kaplan-Meier (KM) and Cox regression analyses.ResultsA total of 173 participants were enrolled in this study. Circulating GAS5 expression was significantly down-regulated in AF patients. This change occurred prior to enlargement of the left atrial volume and was strongly associated with AF progression, which demonstrates the potential use of GAS5 as an early biomarker. The area under the ROC curve (AUC) was 0.858 (95% CI 0.789-0.926, P < .001). Seventy of the 85 AF patients received radiofrequency catheter ablation (RFCA), and 22 (31.4%) had relapsed by the 1-year follow-up. The KM analysis (log-rank test, P = .031) and multivariable Cox analysis (HR = 0.127, 95% CI 0.026-0.616; P = .01) revealed that GAS5 has a role in predicting recurrence after RFCA.ConclusionCirculating lncRNA GAS5 is a potential biomarker for AF diagnosis and prognosis. Down-regulation of GAS5 occurs prior to left atrial enlargement and can be used for the prognosis of AF progression and recurrence.
| S-EPMC7843296 | biostudies-literature
Project description:BackgroundAtrial fibrosis is involved in non-paroxysmal atrial fibrillation (NPAF) and is mainly mediated by the calcium-binding protein S100A4. This study aimed to verify the role of circulating S100A4 in the diagnosis of atrial fibrosis and the prognosis of NPAF.MethodsConsecutive NPAF patients undergoing catheter ablation were selected. Patients with low voltage amplitudes (<0.40 mV) in the left atrium (LA), defined as low voltage zones (LVZs), were grouped in the scar group by electroanatomic mapping (EAM). Circulating S100A4 was detected by a human enzyme-linked immunosorbent assay (ELISA). The role of S100A4 in atrial fibrosis was further evaluated by Masson's trichrome staining and immunochemistry (IHC) in NPAF (atrial pacing) and control dogs. The prognostic value of the circulating S100A4 was evaluated by Cox regression analyses, the Kaplan-Meier (KM) method, and receiver operating characteristic (ROC) curves.ResultsWe enrolled a total of 101 NPAF patients (age 60±8 years) who underwent EAM, including 53 patients with scars and 48 patients without scars at 1-year follow-up. The scar group showed a higher serum level of S100A4 (3.4±1.7 vs. 2.5±1.4 ng/mL, P<0.001) than the non-scar group. In the canine model, scar size matched the larger location of interstitial fibrosis in the NPAF group determined by Masson's trichrome staining. The expression of α-SMA and S100A4 was elevated in the NPAF group as determined by IHC compared to the control group (P<0.001). The clinical recurrence rate was markedly elevated in the scar group (27.1% vs. 8.9%, P<0.001), and the area under the ROC curve was high (0.865, 95% CI: 0.750-0.981) in predicting clinical recurrence of NPAF with the circulating S100A4 model.ConclusionsCirculating S100A4 plays a role in atrial fibrosis in NPAF patients following ablation. The level of serum S100A4 can predict the clinical recurrence of NPAF.
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Project description:BACKGROUND:Nonvalvular atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with the prothrombotic state. Circulating microparticles (cMPs) are membrane vesicles that are shed from many cell types in response to cell activation and cell apoptosis. Several studies reported that cMPs may play a role in the hypercoagulable state that can be observed in patients with AF. The aim of this study was to determine the levels of total cMPs and characterize their cellular origins in AF patients. METHODS:Atotal of 66 AF patients and 33 healthy controls were enrolled. This study investigated total cMP levels and their cellular origin in AF patients using polychromatic flow cytometry. RESULTS:AF patients had significantly higher levels of total cMPs (median 36.38, interquartile range [IQR] 21.16-68.50 × 105 counts/mL vs median 15.21, IQR 9.91-30.86 × 105 counts/mL; P = 0.004), platelet-derived MPs (PMPs) (median 10.61, IQR 6.55-18.04 × 105 counts/mL vs median 7.83, IQR 4.44-10.26 × 10/mL; P = 0.009), and endothelial-derived MPs (EMPs CD31+ CD41-) (median 2.94, IQR 1.78-0.60 × 105 counts/mL vs median 1.16, IQR 0.71-2.30 × 105 counts/mL; P = 0.001) than healthy controls after adjusting for potential confounders. Phosphatidylserine positive MP (PS + MP) levels were similar compared between AF patients and healthy controls. CONCLUSION:The results of this study revealed a marked increase in total cMP levels, and evidence of elevated endothelial damage and platelet activation, as demonstrated by increased PMP and EMP levels, in AF patients. Additional study is needed to further elucidate the role of cMPs (PMPs and EMPs) in the pathophysiology of and the complications associated with AF.
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Project description:Background: Genomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess whether this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation. Methods: mRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAA) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n=83) or in LAA cardiomyocytes (n=52), and combined with clinical parameters to predict AF recurrence. Literature suggests bone morphogenetic protein 10 (BMP10) as a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with eleven cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients. Results: Reduced cardiomyocyte PITX2 concentrations, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, qPCR and Western blotting confirmed BMP10 as one of most PITX2-repressed atrial genes. Left atrial size (hazard ratio per mm increase, HR [95%CI] 1.055 [1.028, 1.082], non-paroxysmal AF (HR 1.672 [1.206, 2.318]) and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed eleven other cardiovascular biomarkers in predicting recurrent AF. Conclusions: Reduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted, atrial protein BMP10 identify patients at risk of recurrent AF after ablation.
2020-06-19 | GSE152181 | GEO
Project description:Atrial fibrillation (AF) is associated with complex and multifaceted etiology including neural modulation that alters atrial electrophysiology. To explore potential biomarkers for AF and AF recurrence. Peripheral histidine levels in PeAF were significantly higher compared to those in the right atrium and coronary sinus. Receiver operating characteristic (ROC) analysis revealed that peripheral histidine was predictive of AF recurrence, with an optimal cutoff value of ≤ 4.71 µg/mL, yielding a sensitivity of 76.3% and a specificity of 76.5%. The area under the ROC curve (AUC) was 0.75 (95% CI, 0.59–0.90). Peripheral His was robustly associated with lower incidence of AF recurrence after covariates adjustment (OR 0.34, 95% CI 0.14- 0.71, p=0.01).
2025-02-14 | GSE289284 | GEO
Project description:Ca2+/calmodulin-dependent kinase II (CaMKII) regulates synaptic plasticity in multiple ways, supposedly including the secretion of neuromodulators like brain-derived neurotrophic factor (BDNF). Here, we show that neuromodulator secretion is indeed reduced in mouse α- and βCaMKII-deficient (αβCaMKII double-knockout [DKO]) hippocampal neurons. However, this was not due to reduced secretion efficiency or neuromodulator vesicle transport but to 40% reduced neuromodulator levels at synapses and 50% reduced delivery of new neuromodulator vesicles to axons. αβCaMKII depletion drastically reduced neuromodulator expression. Blocking BDNF secretion or BDNF scavenging in wild-type neurons produced a similar reduction. Reduced neuromodulator expression in αβCaMKII DKO neurons was restored by active βCaMKII but not inactive βCaMKII or αCaMKII, and by CaMKII downstream effectors that promote cAMP-response element binding protein (CREB) phosphorylation. These data indicate that CaMKII regulates neuromodulation in a feedback loop coupling neuromodulator secretion to βCaMKII- and CREB-dependent neuromodulator expression and axonal targeting, but CaMKIIs are dispensable for the secretion process itself.
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Project description:The aim of this study is to perform transcriptome analysis on mouse left atrium tissue after long-term ibrutinib treatment or cardiac CSK knockout, in order to compared the enriched gene clusters.
2020-04-01 | GSE139427 | GEO
Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation.
Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery.
The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.
| 2312263 | ecrin-mdr-crc
Project description:BACKGROUNDGenomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess if this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation.METHODSmRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAAs) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n = 83) or in LAA cardiomyocytes (n = 52), and combined with clinical parameters to predict AF recurrence. Literature suggests that BMP10 is a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with 11 cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients.RESULTSReduced concentrations of cardiomyocyte PITX2, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, quantitative PCR, and Western blotting confirmed that BMP10 is one of the most PITX2-repressed atrial genes. Left atrial size (HR per mm increase [95% CI], 1.055 [1.028, 1.082]); nonparoxysmal AF (HR 1.672 [1.206, 2.318]), and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed 11 other cardiovascular biomarkers in predicting recurrent AF.CONCLUSIONSReduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted atrial protein BMP10 identify patients at risk of recurrent AF after ablation.TRIAL REGISTRATIONClinicalTrials.gov NCT01091389, NL50069.018.14, Dutch National Registry of Clinical Research Projects EK494-16.FUNDINGBritish Heart Foundation, European Union (H2020), Leducq Foundation.
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