Yinglong Hou

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and adverse outcomes. High‐throughput proteomics offers a promising approach for identifying circulating biomarkers to improve AF risk stratification. This systematic review evaluated cohort studies published from 2010 to 2024 that employed proteomic approaches to investigate associations between circulating proteins and AF incidence. Studies were screened using predefined criteria, and proteins significantly associated with AF in fully adjusted models were extracted. Bioinformatics analyses, including pathway enrichment and protein–protein interaction (PPI) network mapping, were conducted to characterise the implicated biological processes. Proteins reproducibly associated with AF across studies were further evaluated through drug target annotation and assessed for potential causal relationships using Mendelian randomisation (MR). In total, 111 proteins were identified across nine cohorts, with significant enrichment in pathways related to extracellular matrix organisation and cell adhesion. PPI analysis identified interleukin‐6, matrix metalloproteinase‐2 and C‐reactive protein as central network hubs. Thirteen proteins were reproducible across at least two studies, with NT‐proBNP consistently reported in eight cohorts, supporting its role as a robust and reliable biomarker of AF risk. Drug target analysis showed that four proteins—ANGPT‐2, adrenomedullin, GDF15 and PLAUR—are currently under clinical investigation. MR analysis did not confirm causal associations between these proteins and AF, suggesting they may reflect disease‐related processes rather than directly drive AF onset. This review highlights reproducible proteomic biomarkers and their functional networks in AF, providing a foundation for future studies focused on biomarker‐guided prevention and therapeutic development.Trial Registration: PROSPERO number: CRD420251063038

Atrial structural remodeling plays a central role in the development and progression of atrial fibrillation (AF) and significantly influences its course. Hyperlipidemia, a potential contributor to AF, affects cardiac function through multiple pathways. This study aimed to investigate the underlying mechanisms by which high lipid levels promote AF progression. In vitro cell models were established using palmitic acid (PA) stimulation, and in vivo rat models were generated by feeding a high-fat diet (HFD). Proteomic and transcriptomic sequencing analyses were conducted to identify differentially expressed proteins and genes. Extracellular vesicles (EVs) were isolated and characterized by differential centrifugation. Cell proliferation was assessed using EdU incorporation and flow cytometry, while transmission electron microscopy (TEM) was used to observe autophagy. Protein expression was analyzed by immunoblotting, immunohistochemistry, and immunofluorescence. High lipid stimulation significantly increased the expression of tropomyosin 1 (TPM1) in cardiomyocytes, which was transferred to cardiac fibroblasts via EVs, activating the P53/SHISA5 signaling axis and inducing endoplasmic reticulum (ER) stress and autophagy, thereby promoting atrial structural remodeling. Activation of P53 and overexpression of SHISA5 in human cardiac fibroblast (HCF) cells reduced ER stress, autophagy, and fibrosis. Furthermore, ER stress and autophagy markers were significantly elevated in the atrial tissues of HFD-fed rats, while SHISA5 overexpression mitigated these effects. High-fat stimulation may induce atrial fibrosis through the TPM1/P53/SHISA5 axis by modulating the ER stress-autophagy pathway.

Background: Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown. Objectives: The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation. Methods: A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling. Results: The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation. Conclusions: lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.

Background: The utilization of catheter ablation among patients with atrial fibrillation (AF) and heart failure (HF) has garnered significant attention. There has been a rapid proliferation of diverse articles addressing this topic. This study evaluated the potential redundancy in meta-analyses about this subject. Methods: We searched PubMed, Embase, and the Web of Science for meta-analyses comparing catheter ablation with other therapies among patients with AF and HF from the inception date to December 25, 2023. The extracted data encompassed details about the author, country, publication time, journal, pre-registration status, number and type of included studies, primary endpoints, and results. Additionally, we scrutinized whether these meta-analyses referenced, described, or discussed prior relevant meta-analyses, or were cited within prominent international guidelines. Results: A total of 34 meta-analyses were included. Authors predominantly originated from the United States and China. The majority of articles were published in cardiovascular journals without pre-registration. There were two publication peaks, notably in 2018–2019 and 2023. Primary endpoints predominantly focused on all-cause mortality and alterations in left ventricular ejection fraction (LVEF). A consistent trend emerged across most articles, indicating a 40–50% reduction in mortality and a 5–9% elevation in LVEF associated with catheter ablation. Approximately 79.4%, 64.7%, and 50% of the articles respectively cited, described, and discussed previous meta-analyses on the same subject. Only 9 meta-analyses were referenced in impact international guidelines. Conclusions: Our study demonstrates a notable prevalence of redundant meta-analyses within the domain of catheter ablation among patients with AF and HF.

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long‐term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long‐term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high‐throughput sequencing and TMT‐tagged LC‐MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long‐term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long‐term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

Background: Strain analysis of cardiac magnetic resonance imaging (CMR) is important for the prognosis of heart failure (HF). Herein, we aimed to identify the characteristics and prognostic value of strain analysis revealed by CMR in different HF phenotypes.Methods: Participants with HF, including HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction, and controls were enrolled. The baseline information and clinical parameters of participants were collected, and echocardiography and CMR examination were performed. Three-dimensional strain analysis was performed in the left ventricle, right ventricle, left atrium, and right atrium using CMR. A multifactor Cox risk proportional model was established to assess the influencing factors of cardiovascular adverse events in patients with HF.Results: During a median follow-up of 999 days (range: 616–1334), 20.6% of participants (73/354) experienced adverse events (HF readmission and/or cardiovascular death). Univariable Cox regression revealed that a 1% increase in left atrial global longitudinal strain (LAGLS) was associated with a hazard ratio (HR) of 1.21 [95% confidence interval (CI):1.15–1.28; P < 0.001]. Left ventricular global circumferential strain (LVGCS) (HR, 1.18; 95% CI: 1.12–1.24; P < 0.001), and left ventricular global longitudinal strain (LVGLS) (HR, 1.27; 95% CI: 1.20–1.36; P < 0.001) were also associated with HF hospitalizations and cardiovascular deaths. Among clinical variables, hypertension (HR, 2.11; 95% CI: 1.33–13.36; P = 0.002), cardiomyopathy (HR, 2.26; 95% CI: 1.42–3.60; P < 0.001) were associated with outcomes in univariable analysis. Multivariable analyses revealed that LAGLS (95% CI: 1.08–1.29; P < 0.001), LVGLS (95% CI:1.08–1.29; P < 0.001) and LVGCS (95% CI: 1.19–1.51; P < 0.001) were significantly associated with outcomes. Among clinical variables, hypertension (95% CI: 1.09–3.73; P < 0.025) remained a risk factor.Conclusion: CMR plays an obvious role in phenotyping HF. Strain analysis, particularly left atrial and left ventricular strain analysis (LAGLS, LVGLS, and LVGCS) has good value in predicting adverse outcome events.

Background: Autonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention. Methods: Cell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 μm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method. Results: The study found that cardiomyocytes’ mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ). Conclusions: Neural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression.