Testosterone Inhibits Lipid Accumulation in Porcine Preadipocytes by Regulating ELOVL3.

Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and without androgen by adding testosterone exogenously. The fluorescence intensity of lipid droplet (LD) staining and the fatty acid synthetase (FASN) mRNA levels were lower in the testosterone-treated cells than in the untreated control cells. In contrast, the mRNA levels of adipose triglycerides lipase (ATGL) and androgen receptor (AR) were higher than in the testosterone-treated cells than in the control cells. Subsequently, transcriptomic sequencing of porcine preadipocytes incubated with and without testosterone showed that the mRNA expression levels of very long-chain fatty acid elongase 3 (ELOVL3), a key enzyme involved in fatty acids synthesis and metabolism, were high in control cells. The siRNA-mediated knockdown of ELOVL3 reduced LD accumulation and the mRNA levels of FASN and increased the mRNA levels of ATGL. Next, we conducted dual-luciferase reporter assays using wild-type and mutant ELOVL3 promoter reporters, which showed that the ELOVL3 promoter contained an androgen response element (ARE); furthermore, its transcription was negatively regulated by AR overexpression. In conclusion, our study reveals that testosterone inhibits fat deposition in porcine preadipocytes by suppressing ELOVL3 expression. Moreover, our study provides a theoretical basis for further studies on the mechanisms of fat deposition caused by castration.

Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Study on the Characteristics of Coarse Feeding Tolerance of Ding'an Pigs: Phenotypic and Candidate Genes Identification.

Ding'an (DA) pig, a prominent local breed in Hainan Province, exhibits notable advantages in coarse feeding tolerance and high-quality meat. To explore the potential genetic mechanism of coarse feeding tolerance in DA pigs, 60-day-old full sibling pairs of DA and DLY (Duroc-Landrace-Yorkshire) pigs were subjected to fed normal (5%) and high (10%) crude fiber diets for 56 days, respectively. The findings showed that increasing the crude fiber level had no impact on the apparent digestibility of crude fiber, intramuscular fat, and marbling scores in DA pigs, whereas these factors were significantly reduced in DLY pigs (p < 0.05). Through differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) of the colonic mucosal transcriptome data, 65 and 482 candidate genes with coarse feeding tolerance in DA pigs were identified, respectively. Joint analysis screened four key candidate genes, including LDHB, MLC1, LSG1, and ESM1, potentially serving as key regulated genes for coarse feeding tolerance. Functional analysis revealed that the most significant pathway enriched in differential genes associated with coarse feeding tolerance in Ding'an pigs was the signaling receptor binding. The results hold substantial significance for advancing our understanding of the genetic mechanisms governing coarse feeding tolerance in Ding'an pigs.

Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

High blood pressure is associated with increased risk of future fracture, but not vice versa.

The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997-2015 (N = 10,227), 2000-2015 (N = 10,547), 2004-2015 (N = 10,909), and 2006-2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95-1.90) in 1997-2015, 1.40 (1.04-1.88) in 2000-2015, 1.32 (0.98-1.78) in 2004-2015, and 1.38 (1.01-1.88) in 2006-2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96-1.72) in 1997-2015, 1.18 (0.94-1.49) in 2000-2015, 1.12 (0.89-1.40) in 2004-2015, and 1.09 (0.85-1.38) in 2006-2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.

Exosomal CircRNAs in Circulation Serve as Diagnostic Biomarkers for Acute Myocardial Infarction.

BACKGROUND: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. METHODS: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. RESULTS: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. CONCLUSIONS: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

Differential Regulation of Male-Hormones-Related Enhancers Revealed by Chromatin Accessibility and Transcriptional Profiles in Pig Liver.

Surgical castration can effectively avoid boar taint and improve pork quality by removing the synthesis of androstenone in the testis, thereby reducing its deposition in adipose tissue. The expression of genes involved in testis-derived hormone metabolism was altered following surgical castration, but the upstream regulatory factors and underlying mechanism remain unclear. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics in liver tissue of castrated and intact full-sibling Yorkshire pigs. First, we identified 897 differentially expressed genes and 6864 differential accessible regions (DARs) using RNA- and ATAC-seq. By integrating the RNA- and ATAC-seq results, 227 genes were identified, and a significant positive correlation was revealed between differential gene expression and the ATAC-seq signal. We constructed a transcription factor regulatory network after motif analysis of DARs and identified a candidate transcription factor (TF) SP1 that targeted the HSD3B1 gene, which was responsible for the metabolism of androstenone. Subsequently, we annotated DARs by incorporating H3K27ac ChIP-seq data, marking 2234 typical enhancers and 245 super enhancers involved in the regulation of all testis-derived hormones. Among these, four typical enhancers associated with HSD3B1 were identified. Furthermore, an in-depth investigation was conducted on the androstenone-related enhancers, and an androstenone-related mutation was identified in a newfound candidatetypical enhancer (andEN) with dual-luciferase assays. These findings provide further insights into how enhancers function as links between phenotypic and non-coding area variations. The discovery of upstream TF and enhancers of HSD3B1 contributes to understanding the regulatory networks of androstenone metabolism and provides an important foundation for improving pork quality.

Circulating Exosomal CircRNAs as Diagnostic Biomarkers for Chronic Coronary Syndrome.

Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease; however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). High-throughput sequencing was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real-time polymerase chain reaction in a small-sample cohort and a large-sample cohort. A total of 276 circRNAs were differentially expressed in the plasma exosomes of CCS patients, with 103 up-regulated and 173 down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels were selected for validation. Real time quantitative PCR of the first and second validation cohort demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS. Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve values of 0.761 (p < 0.001, 95%CI = 0.669, 0.852) and 0.623 (p = 0.015, 95%CI = 0.522, 0.724) for CCS, respectively, by ROC curve analysis. In conclusion, the expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS.

Circulating exosomal lncRNAs in patients with chronic coronary syndromes.

Introduction: The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods: A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results: A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions: Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

Effect of ApoE ε4 gene polymorphism on the correlation between serum uric acid and left ventricular hypertrophy remodeling in patients with coronary heart disease.

Background: Hyperuricemia and dyslipidemia are associated with left ventricular hypertrophy (LVH), while the effect of ApoE gene polymorphism on the correlation between serum uric acid (UA) level and severity of LVH in patients with coronary heart disease (CHD) has not been clarified. Methods: This was a retrospective observational study of patients with CHD. Patients were divided into groups of ε4 carriers and non-ε4 carriers based on sanger sequencing. The association of ApoE ε4 gene polymorphism, serum UA level, and LVH, determined by cardiac color Doppler ultrasound, was evaluated by multivariate analysis. Results: A total of 989 CHD patients who underwent ApoE genotyping were enrolled and analyzed. Among them, the frequency of the ApoE ε4 genotype was 17.9% (15.7% for E3/4, 1.1% for E4/4, and 1.1% for E2/4). There were 159 patients with LVH, 262 with end-diastolic LV internal diameter (LVEDD) enlargement, 160 with left ventricular ejection fraction (LVEF) reduction, and 154 with heart failure. Multivariate analysis showed that for every increase of 10 µmol/L in serum UA level, the risk of LVH decreased in ε4 carriers (odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.890-0.992, P = 0.025) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.005-1.049, P = 0.016). The risk of LVEDD enlargement tended to decrease in ε4 carriers (OR = 0.98, 95% CI: 0.943-1.023, P = 0.391) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.009-1.048, P = 0.003). The risk of LVEF reduction was reduced in ε4 carriers (OR = 0.996, 95% CI: 0.949-1.046, P = 0.872) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.994-1.037, P = 0.17). The risk of LVEDD enlargement decreased in ε4 carriers (OR = 0.98, 95% CI: 0.931-1.036, P = 0.508) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.998-1.042, P = 0.07). Conclusion: High serum UA levels decreased the risk of LVH in ApoE ε4 carriers with CHD, while increased the risk of LVH in non-ε4 carriers.

Elevated plasma Sirtuin2 level predicts heart failure after acute myocardial infarction.

BACKGROUND: There is currently no evidence regarding the role of plasma Sirtuin2 (SIRT2) level in acute myocardial infarction (AMI) yet. This study assessed the role of plasma SIRT2 in AMI, and investigated the association of plasma SIRT2 level with major adverse cardiovascular events (MACE) and heart failure after AMI. METHODS: This is a prospective observational study. A total of 129 AMI patients (mean age: 62.2±12.7 years old, male/female: 96/33) were included. Cox proportional hazards regression models were used to estimate the association of different SIRT2 levels with MACE and heart failure after AMI. RESULTS: According to the 75th percentile value of plasma SIRT2 level, we divided all the AMI patients into two groups: high-level group (plasma SIRT2 level ≥109.0 pg/mL) and low-level group (plasma SIRT2 level <109.0 pg/mL). Compared with the low-level group, the high-level group had higher percentage of Killip class ≥3 (P<0.001), left ventricular ejection fraction (LVEF) <50% (P=0.007) or even <40% (P=0.012), use of breathing machine(P=0.003), and higher plasma brain natriuretic peptide (BNP) level (P=0.006). Multivariate Cox regression analysis showed that there were higher risks of MACE [hazard ratio (HR) 11.20, 95% confidence interval (CI): 3.18-39.52, P<0.001)] and heart failure (HR 27.10, 95% CI: 4.65-157.83, P<0.001) in the high-level group. CONCLUSIONS: The present study suggested that plasma SIRT2 level is a promising biomarker to predict heart failure and MACE after AMI.

Expression profile of circular RNAs in epicardial adipose tissue in heart failure.

BACKGROUND: Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups. METHODS: RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test. RESULTS: A total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively. CONCLUSION: These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.

Circulating exosomal long non-coding RNAs in patients with acute myocardial infarction.

Exosomes are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized in acute myocardial infarction (AMI). However, the regulatory role of exosomal long non-coding RNAs (lncRNAs) in AMI remains largely unclear. Exosomes were isolated from the plasma of AMI patients and controls, and the sequencing profiles and twice qRT-PCR validations of exosomal lncRNAs were performed. A total of 518 differentially expressed lncRNAs were detected over two-fold change, and 6 kinds of lncRNAs were strikingly elevated in AMI patients with top fold change and were selected to perform subsequent validation. In the two validations, lncRNAs ENST00000556899.1 and ENST00000575985.1 were significantly up-regulated in AMI patients compared with controls. ROC curve analysis revealed that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 yielded the area under the curve values of 0.661 and 0.751 for AMI, respectively. Moreover, ENST00000575985.1 showed more significant relationship with clinical parameters, including inflammatory biomarkers, prognostic indicators and myocardial damage markers. Multivariate logistic model exhibited positive association of ENST00000575985.1 with the risk of heart failure in AMI patients. In summary, our data demonstrated that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 are elevated in patients with AMI, functioning as potential biomarkers for predicting the prognosis of pateints with AMI.

Proteomics of epicardial adipose tissue in patients with heart failure.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non-HF patients as controls. A total of 771 proteins were identified in liquid chromatography-tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF-related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up-regulated in HF, with HF/non-HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.

Circulating Serpina3 levels predict the major adverse cardiac events in patients with myocardial infarction.

BACKGROUND: Serine proteinase inhibitor A3 (Serpina3), initially discovered as an acute phase plasma protease inhibitor, has been demonstrated in the pathology of complex human disorders, but it is yet to be discovered following acute myocardial infarction (AMI) in clinical practice. Therefore, we aimed to evaluate the relationship between Serpina3 concentrations at admission and the risk of major adverse cardiovascular events (MACE) in patients with AMI. METHODS: A total of 120 AMI patients and 60 healthy participants were consecutively enrolled in our study. Clinical parameters variables were collected, and MACE was followed since hospitalization. RESULTS: Plasma concentrations of Serpina3 were elevated after AMI [159.11 (121.81, 237.07) vs. 300.18 (187.90, 478.59) µg/mL, P < 0.001]. Multivariate linear regression analysis indicated that total cholesterol (standardized ß = -0.204, P = 0.024) and ESR (standardized ß = 0.513, P < 0.001) were independent factors for Serpina3. Based on the median value of Serpina3 in the AMI population, patients were divided into the high-Serpina3 group (≥300.18 µg/mL, n = 65) and the low-Serpina3 group (<300.18 µg/mL, n = 60). After a median follow-up of 9 months, Kaplan-Meier survival analysis revealed that the MACE-free survival rate was significantly lower in AMI patients with higher Serpina3 levels (P = 0.002). Multivariate Cox proportional hazards analyses demonstrated that Serpina3 was a positive predictor of MACE (hazard ratios 4.03, 95% CI 1.25-12.98, P = 0.019). CONCLUSIONS: Increased circulating Serpina3 levels following AMI is significantly associated with MACE, which suggest that Serpina3 may be a potential predictive marker of clinical outcomes in AMI.

Analysis of long non-coding RNA and mRNA profiles in epicardial adipose tissue of patients with atrial fibrillation.

Accumulating studies have suggested that epicardial adipose tissue (EAT) play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying long non-coding RNAs (lncRNAs), may modulate atrial remodeling. LncRNAs are associated with cardiovascular disorders, including AF, but their roles in EAT remain elusive. The aim of the present study was to investigate the expression profile of lncRNAs in EAT with AF. Differentially expressed lncRNAs and nearby mRNAs interaction networks were constructed. Epicardial adipose samples were collected from patients with persistent non-valvular AF (n = 6) and sinus rhythm (SR) (n = 6), and the expression of lncRNAs and mRNAs were profiled using RNA-sequencing method. A total of 46,577 transcripts, including 35,552 protein-coding pattern, corresponding to 15,404 genes in EAT, among which, 655 mRNAs (265 upregulated and 390 downregulated) and 57 lncRNAs (17 upregulated and 40 downregulated) were differentially expressed between AF and SR (P < 0.05; fold change>1.5). GO enrichment, KEGG pathway analysis and interaction network construction showed that these differentially expressed lncRNAs were enriched in functional categories, including metabolism and stress response, which might contribute to the pathogenesis of AF. Our study demonstrated a differentially expressed lncRNA profile in EAT with AF, and provide a novel insight into the interactions between EAT and AF.

Expression Profiles of Long Noncoding RNA and mRNA in Epicardial Adipose Tissue in Patients with Heart Failure.

The expression profile of long noncoding RNA (lncRNA) in human epicardial adipose tissue (EAT) has not been widely studied. In the present study, we performed RNA sequencing to analyze the expression profiles of lncRNA and mRNA in EAT in coronary artery disease (CAD) patients with and without heart failure (HF). Our results showed RNA sequencing disclosed 35673 mRNA and 11087 lncRNA corresponding to 15554 genes in EAT in total, while 30 differentially expressed lncRNAs (17 upregulated and 13 downregulated) and 278 differentially expressed mRNAs (129 upregulated and 149 downregulated) were discriminated between CAD patients with and without HF (P<0.05; fold change>2); lncRNA ENST00000610659 drew specific attention for it was the top upregulated lncRNA with highest fold change and corresponded to UNC93B1 gene, which was proved to be related to HF and encoded UNC93B1 protein regulating toll-like receptor signaling, and both of them significantly increased in HF patients in qRT-PCR validation; the top significant upregulated enriched GO terms and KEGG pathway analysis were regulation of lymphocyte activation (GO:0051249) and T cell receptor signaling pathway (hsa04660), respectively. The current findings support the fact that EAT lncRNAs are involved in the inflammatory response leading to the development of HF.

Correlation of triglycerides with myocardial infarction and analysis of risk factors for myocardial infarction in patients with elevated triglyceride.

BACKGROUND: This study aims to investigate the associations of different (low/medium/high) levels of fasting triglyceride (TG) levels with cardiovascular endpoints. METHODS: This cohort study comprised of in-service and retired employees of the Kailuan Coal Mine Group, who participated in the health examination conducted in 11 hospitals in the Kailuan region from June 2006 to October 2007 (n=100,271). The study population was divided into five groups according to different TG levels. Logistic regression analysis was used to analyze the risk factors for myocardial infarction (MI) in patients with elevated TG, and Cox proportional hazards regression analysis was used to analyze the effects of different TG levels on endpoint events. RESULTS: After a median follow-up of 7 years, 961 patients developed MI and 3,142 subjects died. The multivariate logistic regression analysis revealed that elevated TG, an age of ≥65 years old, body mass index (BMI) >25 kg/m2, fasting blood glucose (FBG) ≥6.1 mmol/L and high density lipoprotein cholesterol (HDL-C) <1.5 mmol/L were all risk factors for MI (P<0.05). Furthermore, Cox proportional hazards regression model revealed that after controlling for gender, age and other factors, with the increase in TG level, the relative risk of MI also increased. Compared to the TG1 group, the risk of MI increased to 1.32 folds in the TG4 group (95% CI: 1.05-1.66, P=0.018) and 1.61 folds in the TG5 group (95% CI: 1.21-1.93, P=0.004). Furthermore, the risk of MI combined with all-cause death and all-cause death also increased, but the differences were not all statistically significant. CONCLUSIONS: In the study population of the Kailuan region, elevated fasting TG increases the risk of MI, particularly in populations with an age of ≥65 years old, BMI >25 kg/m2, FBG ≥6.1 mmol/L and HDL-C <1.5 mmol/L.

Effect of remote ischemic preconditioning on left atrial remodeling and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is known to induce left atrial remodeling and prothrombotic response. AIMS: This study aimed to evaluate the effect of remote ischemic preconditioning (RIPC) on left atrial remodeling and prothrombotic response induced by RFCA of AF. METHODS: Forty-four patients with drug-refractory paroxysmal AF undergoing RFCA were randomized into RIPC (four short episodes of forearm ischemia) and control groups before the procedure. Blood samples were collected before RIPC/sham RIPC, and 24 and 72 hours later after the procedure. The atrial remodeling marker matrix metalloproteinase-9 (MMP-9) and endothelial damage marker von Willebrand factor (vWF) were measured using enzyme-linked immunosorbent assay. Platelet activation was evaluated by flow cytometric measurements of the expression of platelet P-selectin (CD62P) and active glycoprotein IIb/IIIa receptor (PAC-1). The early recurrence of atrial fibrillation (ERAF) in the two groups was observed over the subsequent 3 months. RESULTS: RFCA resulted in a significant increase in MMP-9 and vWF in both the groups, which persisted for 72 hours. However, the expression of CD62P and PAC-1 showed less increase during RFCA in either group. The RIPC group showed a lower increase in MMP-9 and vWF compared with the control group. In contrast, no significant differences were found in the trend of expression of CD62P and PAC-1 during RFCA between the two groups. The AF recurrence in the 3 months after the ablation was significantly lower in the RIPC group than in the control group. CONCLUSIONS: RIPC before RFCA for paroxysmal AF significantly reduces the increase in markers of left atrial remodeling and endothelial damage associated with the procedure, and results in a lower ERAF.

miR-483-3p regulates acute myocardial infarction by transcriptionally repressing insulin growth factor 1 expression.

The aim of the present study was to evaluate the functional association between the expression of miR­483­3p and acute myocardial infarction (AMI) in patients and in vitro. H9c2 cells were incubated in a vacuum with 5% CO2, 5% H2 and 90% N2 for 2 h, which generated the AMI model in vitro. Reverse transcription­quantitative polymerase chain reaction was used to measure miR­483­3p expression, and flow cytometry analysis and ELISA analysis were used to analyze apoptosis rate via caspase­3 and caspase­9 activity kits. B­cell lymphoma 2 (Bcl­2)/Bcl­2­associated X protein (Bax) and transcriptionally suppressed the protein expression of insulin growth factor 1 (IGF­1) were analyze using western blot analysis. The results demonstrated that the expression of miR­483­3p in patients with AMI was increased when compared with the control group. In the in vitro model, the overexpression of miR­483­3p promoted apoptosis, increased caspase­3 and caspase­9 activity levels, induced the protein expression of Bcl­2/Bax and IGF­1. Picropodophyllotoxin, an IGF­1 inhibitor, was administered to cells following the overexpression of miR­483­3p. Administration of picropodophyllotoxin suppressed IGF­1 protein expression, promoted apoptosis, increased caspase­3 and caspase­9 activity levels, and induced the protein expression of Bax/Bcl­2. The results of the present study revealed that miR­483­3p may regulate AMI via the IGF­1 signaling pathway and may support the restoration of functional performance following AMI.