Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

Long noncoding RNA and messenger RNA profiling in epicardial adipose tissue of patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) constitutes a significant complication following coronary artery bypass graft surgery (CABG), potentially linked to epicardial adipose tissue (EAT). This investigation seeks to elucidate the association between POAF and EAT at the genetic level. METHODS: EAT and clinical data from patients undergoing CABG were systematically acquired, adhering to established inclusion and exclusion criteria. Patients were categorized into POAF and Non-POAF groups based on the presence or absence of POAF. High-throughput sequencing data of EAT were subjected to differential expression analysis and gene function assessment. A random selection of long noncoding RNAs (lncRNAs) underwent quantitative real-time polymerase chain reaction (qRT-PCR) for validation of the high-throughput sequencing findings. Coexpression analysis was employed to elucidate the interactions between lncRNAs and messenger RNAs (mRNAs). RESULTS: RNA sequencing yielded a total of 69,685 transcripts (37,740 coding and 31,945 noncoding sequences), representing 16,920 genes. Within this dataset, 38 mRNAs and 12 lncRNAs exhibited differential expression between the POAF and Non-POAF groups (P < 0.05, fold change > 1.5). The qRT-PCR results for lncRNAs corroborated the sequencing findings (P < 0.01). Functional enrichment analysis of genes and the coexpression network indicated that these differentially expressed RNAs were primarily implicated in processes such as cell growth, differentiation, signal transduction, as well as influencing tissue fibrosis and ion transmembrane transport. CONCLUSIONS: This study unveils a potential association between myocardial fibrosis and ion channels co-regulated by mRNAs and lncRNAs, closely linked to the emergence of new-onset POAF, after accounting for clinical risk factors. This discovery holds promise for further advances in clinical and fundamental research.

Expression profiles and functional analysis of tRNA-derived small RNAs in epicardial adipose tissue of patients with heart failure.

BACKGROUND: Heart failure is considered an epidemic disease in the modern world. Since it presents as a multifactorial, systemic disease, a comprehensive understanding of the underlying mechanism is essential. Epicardial adipose tissue (EAT) is increasingly recognized to be metabolically active and is able to secrete myriad bioactive molecules, including exosomes carrying tRNA-derived small RNAs (tsRNAs). Mounting evidence has suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but no studies have focused on the influence of tsRNA in EAT on cardiac dysfunction. METHODS: To investigate the regulatory mechanism of tsRNAs of EAT associated with HF, we collected EAT from HF (n = 5) patients and controls (n = 5) and used a combination of RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and bioinformatics to screen the expression profiles of tsRNAs in HF. RESULTS: We ultimately identified an expression profile of 343 tsRNAs in EAT. Of those, a total of 24 tsRNAs were significantly differentially expressed between HF and controls: 17 were upregulated and 7 were downregulated (fold change >1.5, p < 0.05). Four tsRNAs (tiRNA-Pro-TGG-001, tRF-Met-CAT-002, tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011) were randomly selected and validated by qRT-PCR. Bioinformatics analyses revealed a dense interaction of target genes between tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011. Based on functional analysis, these two tRFs might play a protective role by regulating sphingolipid and adrenergic signaling pathways by targeting genes mainly contributing to calcium ion transport. CONCLUSIONS: Our study profiled tsRNA expression in EAT with HF and identified a comprehensive dimension of potential target genes and tsRNA-mRNA interactions.

The development of heart failure involves a complex mechanistic network, which until now, has not been clarified.Excess epicardial adipose tissue may promote heart failure via unknown mechanisms.Our current study profiled transfer RNAs expression in epicardial adipose tissue with heart failure and identified a comprehensive dimension of potential target genes and transfer RNAs -mRNA interactions for the pathogenesis of deterioration in cardiac function.

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction.

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography-tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

Declined plasma microfibrillar-associated protein 4 levels in acute coronary syndrome.

BACKGROUND: Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. METHODS: We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan-Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. RESULTS: Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174-0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = - 0.311 and - 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan-Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009). CONCLUSIONS: MFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted.

The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia that affects approximately 1-2% of the general population. The mechanism of AF pathogenesis remains unclear. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been shown to be closely related to AF. EAT has a biological impact on neighboring myocardium by producing a myriad of bioactive molecules, including exosomes carrying circular RNAs (circRNAs). As a new category of noncoding RNAs, circRNAs can work as efficient sponges for specific microRNAs and efficiently regulate gene expression. MATERIAL AND METHODS: To investigate the regulatory mechanism of circRNAs of EAT in patients with AF, we collected EAT from AF (n=6) patients and non-AF (n=6) controls and profiled their circRNA expression with the RNA-sequencing method. RESULTS: RNA sequencing detected a total of 2159 circRNAs in EAT, among which 528 were upregulated and 579 were downregulated. The top highly expressed EAT circRNAs corresponded to genes involved in inflammation and cell proliferation, including SUPT5H, CCDC62, DPY19L1P1, RASGRP1, AP3S1, CGNL1, KAT2B, BNIP2, and SACS. The top three circRNAs with higher FCs (fold changes) were hsa_circ_0099634, hsa_circ_0000932 and hsa_circ_0097669 (FC=25.6), while lower FCs were identified in hsa_circ_0135289, hsa_circ_0098155 and hsa_circ_0079672. A network involving these noncoding RNAs and mRNAs was also constructed to predict their potential biological functions in the pathology of AF. CONCLUSIONS: Our study provided novel insight into EAT's roles in AF and proposed interactions, including possible mediators.

Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study.

BACKGROUND: Hyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB. METHODS: From December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant. RESULTS: Thirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145-1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876-10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709-9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB. CONCLUSIONS: Hyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.