Dataset Information

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

ABSTRACT:

Background

Correlations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease.

Methods

Through LC-MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored the ubiquitination profiles of left atrial appendage samples.

Results

In summary, after the quantification ratios for the upregulated and downregulated ubiquitination cutoff values were set at >1.5 and <1:1.5, respectively, a total of 271 sites in 162 proteins exhibiting upregulated ubiquitination and 467 sites in 156 proteins exhibiting downregulated ubiquitination were identified. The ubiquitylated proteins in the AF samples were enriched in proteins associated with ribosomes, hypertrophic cardiomyopathy (HCM), glycolysis, and endocytosis.

Conclusions

Our findings can be used to clarify differences in the ubiquitination levels of ribosome-related and HCM-related proteins, especially titin (TTN) and myosin heavy chain 6 (MYH6), in patients with AF, and therefore, regulating ubiquitination may be a feasible strategy for AF.

SUBMITTER: Wu CK

PROVIDER: S-EPMC10493305 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

Wu Chen-Kai CK Teng Shuai S Bai Fan F Liao Xiao-Bo XB Zhou Xin-Min XM Liu Qi-Ming QM Xiao Yi-Chao YC Zhou Sheng-Hua SH

Frontiers in cardiovascular medicine 20230828

<h4>Background</h4>Correlations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease.<h4>Methods</h4>Through LC-MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored ...[more]

PMID: 37701139

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Project description:BackgroundSurgical left atrial appendage occlusion (SLAAO) may be associated with a lower risk of thromboembolism in patients with atrial fibrillation undergoing cardiac surgery. However, evidence regarding the effectiveness of SLAAO in patients undergoing mechanical heart valve replacement (MHVR) is lacking. Therefore, we aimed to evaluate the association between SLAAO and the cardiovascular outcomes in patients with atrial fibrillation undergoing MHVR.MethodsWe retrospectively analyzed data for 497 patients with atrial fibrillation; 27.6% of the patients underwent SLAAO, and the remainder of the patients did not (No-SLAAO group). The primary outcome was a composite of ischemic stroke, systemic embolism, and all-cause mortality. Cumulative event-free survival rates were estimated using Kaplan-Meier curves, and we performed multivariate Cox analyses to evaluate the association between SLAAO and outcomes. We used one-to-one propensity score matching to balance patients' baseline characteristics, and analyzed 120 matching pairs.ResultsFive patients died within 30 days postoperatively, and there were no significant differences between the two groups regarding in-hospital complications (all P > 0.05). After a median follow-up of 14 months, 14 primary events occurred. Kaplan-Meier curves showed no difference in the cumulative incidence of freedom from the primary outcome (log-rank P = 0.830), hemorrhagic events (log-rank P = 0.870), and the secondary outcome (log-rank P = 0.730), between the two groups. Multivariable Cox proportional hazards regression analysis showed no association between SLAAO and any outcome (all P > 0.05). After propensity score matching, cardiopulmonary bypass time and aortic cross-clamp time, and the postoperative length of stay were significantly longer in the SLAAO group (all P < 0.05); results were similar to the unadjusted analyses.ConclusionsConcomitant SLAAO and MHVR was associated with longer length of stay, and cardiopulmonary bypass time and aortic cross-clamp time, but was not associated with additional protective effects against thromboembolic events and mortality during the 14-month follow-up.

Project description:BackgroundNumerous basic studies have demonstrated critical roles of metabolic and contractile remodeling in pathophysiological changes of atrial fibrillation (AF), but acetylation changes underlying atrial remodeling have not been fully elucidated. Quantitative acetylated proteomics enables researchers to identify a comprehensive map of protein alterations responsible for pathological development and progression of AF in the heart of patients.Materials and methodsIn this study, 18 samples (9 with chronic AF and 9 with sinus rhythm) of left atrial appendage (LAA) tissues were obtained during mitral valve replacement surgery. Changes in the quantitative acetylated proteome between the AF and sinus rhythm (SR) groups were studied by dimethyl labeling, acetylation affinity enrichment, and high-performance liquid chromatography-tandem mass spectrometry analysis.ResultsWe identified a total of 5,007 acetylated sites on 1,330 acetylated proteins, among which 352 acetylated sites on 193 acetylated proteins were differentially expressed between the AF and SR groups by setting a quantification ratio of 1.3 for threshold value and P < 0.05 for significant statistical difference. The bioinformatics analysis showed that the differentially expressed acetylated proteins were mainly involved in energy metabolism and cellular contraction and structure function-related biological processes and pathways. Among 87 differentially expressed energy metabolism acetylated proteins related to the processes of fatty acid, carbohydrate, ketone body metabolism, and oxidative phosphorylation, nearly 87.1% Kac sites were upregulated (148 Kac sites among 170) in the AF group. Besides, generally declining acetylation of cardiac muscle contraction-related proteins (88.9% Kac sites of myosin) was found in the LAA of patients with AF. Immune coprecipitation combined with Western blotting was conducted to validate the differential expression of acetylated proteins.ConclusionMany differentially expressed energy metabolism and cellular contraction acetylated proteins were found in the LAA tissues of patients with chronic AF, and may reflect the impaired ATP production capacity and decreased atrial muscle contractility in the atrium during AF. Thus, acetylation may play an important regulatory role in metabolic and contractile remodeling of the atrium during AF. Moreover, the identified new acetylated sites and proteins may become promising targets for prevention and treatment of AF.

Project description:BackgroundManaging patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF.MethodsAF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison.ResultsAmong 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores.ConclusionsCombining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Dataset Information

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

Background

Methods

Results

Conclusions

Publications

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

Similar Datasets

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