Mechanism of myocardial fibrosis regulation by IGF-1R in atrial fibrillation through the PI3K/Akt/FoxO3a pathway.

Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen Ⅰ protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway.

Differential Proteomic Profiles of Coronary Serum Exosomes in Acute Myocardial Infarction Patients with or Without Diabetes Mellitus: ANGPTL6 Accelerates Regeneration of Endothelial Cells Treated with Rapamycin via MAPK Pathways.

PURPOSE: Delayed re-endothelialization after coronary drug-eluting stent implantation is associated with an increased incidence of late in-stent thrombosis. Serum exosomes exhibit controversial effects on promoting endothelialization. This study aimed to compare the angiogenic effects of serum exosomes derived from patients with acute myocardial infarction (AMI) and AMI plus diabetes mellitus (DM) and to explore the underlying mechanisms. METHODS: Serum exosomes derived from patients in the control (Con-Exos), AMI (AMI-Exos), and AMI plus DM (AMI+DM-Exos) groups were isolated and identified using standard assays. CCK-8, wound healing, and tube formation assays were performed to detect the angiogenic abilities of serum exosomes on rapamycin-conditioned human umbilical vein endothelial cells (HUVECs). Differential proteomic profiles between AMI-Exos and AMI+DM-Exos were analyzed by mass spectrometry. The effects and potential mechanisms of exosomal angiopoietin-like 6 (ANGPTL6) were investigated. RESULTS: Functional assays indicated that compared with Con-Exos, AMI-Exos enhanced, whereas AMI+DM-Exos inhibited the cell proliferation, migration, and tube formation of rapamycin-conditioned HUVECs. Subsequently, 28 differentially expressed proteins between AMI-Exos and AMI+DM-Exos were identified, which were correlated with material transportation, immunity, and inflammatory reaction. Moreover, ANGPTL6 was highly enriched in AMI-Exos. Overexpression and knockdown of ANGPTL6 enhanced and inhibited angiogenesis, respectively. Furthermore, the effect of ANGPTL6 on angiogenesis was mediated via the activation of ERK 1/2, JNK, and p38 pathways. The inhibition of ERK 1/2 signaling markedly attenuated the migration abilities of overexpressing ANGPTL6. CONCLUSION: Diabetes impairs the regenerative capacities of serum exosomes. Exosomal ANGPTL6 contributes to endothelial repair and is a novel therapeutic target for enhanced stent endothelization.

Succinate/IL-1ß Signaling Axis Promotes the Inflammatory Progression of Endothelial and Exacerbates Atherosclerosis.

Inflammation is an important driver of atherosclerosis. Succinate is a new extracellular inflammatory alarm released by activated macrophages. Succinate is sensed by succinate receptor 1 (Sucnr1) and then transferred to effector cells. It is worth exploring whether succinate is capable of facilitating the inflammatory response in atherosclerosis. In this study, we firstly found that arterial serum of Coronary Heart Disease (CHD) patients contained significantly higher succinate and interleukin (IL)-1ß than Health control (HC) subjects, and succinate was positively correlated with IL-1ß. As demonstrated by the in vitro study, succinate/hypoxia-inducible factor 1α (Hif)-1α/IL-1ß signal axis existed and significantly facilitated the inflammatory program in human umbilical vein endothelial cells (HUVECs). Under the coculture, activated macrophages released succinate, which would be transferred to HUVECs via Sucnr1 and then activate Hif-1α to produce a greater amount of IL-1ß. Likewise, the aortic sinus's inflammatory phenotype was found to be more significant within Apoe-/- mice that were injected with succinate. Furthermore, Sucnr1 inhibitor (NF-56-EJ40) could significantly interrupt succinate/IL-1ß signal in HUVECs and macrophages. As revealed by this study, glycolytic metabolism following the release of succinate could be found in atherosclerotic pathology, and succinate would drive succinate/IL-1ß signal dependent on Sucnr1 and then exacerbate inflammatory responses. Sucnr1 might be a novel target for cutting off the transduction of succinate signal to prevent the inflammation of atherosclerosis.

Ivabradine and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: This was a meta-analysis of randomized control trials (RCTs) to evaluate the effect of ivabradine on the risk of atrial fibrillation (AF) and its effect on the ventricular rate in patients with AF. The PubMed, EMBASE, Cochrane Controlled Trials Register, and other databases were searched for RCTs on ivabradine. Thirteen trials with 37,533 patients met the inclusion criteria. The incidence of AF was significantly higher in the ivabradine treatment group than in the control group [odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08-1.41], although it was reduced after cardiac surgery (OR, 0.70; 95% CI, 0.23-2.12). Regarding left ventricular ejection fraction (LVEF), ivabradine increased the risk of AF in both LVEF >40% (OR, 1.42; 95% CI, 1.24-1.63) and LVEF ≤40% subgroups (OR, 1.16; 95% CI, 0.98-1.37). The risk of AF was increased by both small and large cumulative doses of ivabradine (small cumulative dose: OR, 3.00; 95% CI, 0.48-18.93; large cumulative dose: OR, 1.05; 95% CI, 0.83-1.34). Furthermore, ivabradine may reduce the ventricular rate in patients with AF. In conclusion, we found that both large and small cumulative doses of ivabradine were associated with an increased incidence of AF, and the effect was more marked in the LVEF >40% subgroup. Nevertheless, ivabradine therapy is beneficial for the prevention of postoperative AF. Furthermore, ivabradine may be effective in controlling the ventricular rate in patients with AF, although more RCTs are needed to support this conclusion.

Permeation by Electrowetting Actuation: Revealing the Prospect of a Micro-valve Based on Ionic Liquid.

The electrowetting behavior of ionic liquid significantly promotes microfluidic technology due to the advantage of manipulation of ionic liquid without additional mechanical parts. Recently, a novel micro-valve that shows good prospects was proposed by MacArthur et al. based on the permeation of ionic liquid under electric field. Inspired by their work, the permeation process of ionic liquid (EMIM-Im) droplets actuated by electrowetting was investigated in this work using molecular dynamics simulation. The wettability of substrate, electric field strength and electric field polarity were varied to investigate their influences. On the substrate side, results showed that the hydrophilic substrates tend to stretch and adsorb the droplet and hence hinder the permeation process, whereas the hydrophobic substrates facilitate permeation due to their low attraction for liquid. Particularly, super hydrophilic substrates should be avoided in practice, because their strong adsorption effects will override the electric field effects and disable the permeation process. On the electric field side, results showed that increased electric field strength enhances the permeation, but varying electric field polarity will result in an asymmetric permeation behavior, which was found to be the result of the different evaporation rate of the ion species that ultimately caused a non-charge-neutral droplet. Our investigation then uncovered the two critical roles of the electric field: elongating the droplet and providing the driving force for the permeation.

Association of dipeptidyl peptidase IV polymorphism, serum lipid profile, and coronary artery stenosis in patients with coronary artery disease and type 2 diabetes.

ABSTRACT: Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.

Exosomes secreted from mesenchymal stem cells mediate the regeneration of endothelial cells treated with rapamycin by delivering pro-angiogenic microRNAs.

Delayed endothelial healing after drug eluting stent (DES) implantation is a critical clinical problem in treatment of coronary artery diseases. Exosomes exhibit proangiogenic potential in a variety of ischemic diseases. However, the association of exosomes with endothelial regeneration after DES implantation has been rarely reported. In this study, we aimed to investigate the therapeutic effects of mesenchymal stem cell (MSC)-derived exosomes on endothelial cells treated with rapamycin and explore the potential mechanisms of MSC-derived exosomes in promoting endothelial regeneration. Exosomes were isolated from MSCs by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay. The in vitro effects of MSC-derived exosomes on the proliferation and migration of endothelial cells treated with rapamycin were evaluated by integrated experiment, cell counting kit-8, scratch, tube formation, and transwell assays. And the apoptosis of rapamycin-induced endothelial cells loaded with MSC-derived exosomes was detected using TUNEL and Annexin-V FITC and PI double-staining assays. The microRNA (miRNA) cargo of MSC-derived exosomes was identified by high-throughput RNA sequencing. Pro-angiogenic miRNAs and key pathways were further characterized. Our results indicated that MSC-derived exosomes could be ingested into umbilical vein endothelial cells (HUVECs) and significantly enhanced cell proliferation rate, migratory and tube-forming capabilities in vitro. MSC-derived exosomes also inhibited the apoptosis of HUVECs induced by rapamycin. A distinct class of exosomal miRNAs was further identified, including six miRNAs tightly related to neovasculogenesis. Silencing the expression of exosomal miRNA-21-5p and let-7c-5p attenuated the pro-proliferative and pro-migratory capacity of MSC-derived exosomes. Moreover, functional enrichment analysis indicated that metabolic pathways might contribute to reendothelialization. This study highlights a proregenerative effect of MSC-derived exosomes in vitro, which may be partly explained by the delivery of pro-angiogenic miRNAs to endothelial cells.

Plasma-based multi-reforming for Gas-To-Liquid: tuning the plasma chemistry towards methanol.

Because of its unique properties, plasma technology has gained much prominence in the microelectronics industry. Recently, environmental and energy applications of plasmas have gained a lot of attention. In this area, the focus is on converting CO2 and reforming hydrocarbons, with the goal of developing an efficient single-step 'gas-to-liquid' (GTL) process. Here we show that applying tri-reforming principles to plasma-further called 'plasma-based multi-reforming'-allows us to better control the plasma chemistry and thus the formed products. To demonstrate this, we used chemical kinetics calculations supported by experiments and reveal that better control of the plasma chemistry can be achieved by adding O2 or H2O to a mixture containing CH4 and CO2 (diluted in N2). Moreover, by adding O2 and H2O simultaneously, we can tune the plasma chemistry even further, improving the conversions, thermal efficiency and methanol yield. Unlike thermocatalytic reforming, plasma-based reforming is capable of producing methanol in a single step; and compared with traditional plasma-based dry reforming, plasma-based multi-reforming increases the methanol yield by more than seven times and the thermal efficiency by 49%, as revealed by our model calculations. Thus, we believe that by using plasma-based multi-reforming, 'gas-to-liquid' conversion may be made efficient and scalable.

Gliding Arc Plasmatron: Providing an Alternative Method for Carbon Dioxide Conversion.

Low-temperature plasmas are gaining a lot of interest for environmental and energy applications. A large research field in these applications is the conversion of CO2 into chemicals and fuels. Since CO2 is a very stable molecule, a key performance indicator for the research on plasma-based CO2 conversion is the energy efficiency. Until now, the energy efficiency in atmospheric plasma reactors is quite low, and therefore we employ here a novel type of plasma reactor, the gliding arc plasmatron (GAP). This paper provides a detailed experimental and computational study of the CO2 conversion, as well as the energy cost and efficiency in a GAP. A comparison with thermal conversion, other plasma types and other novel CO2 conversion technologies is made to find out whether this novel plasma reactor can provide a significant contribution to the much-needed efficient conversion of CO2 . From these comparisons it becomes evident that our results are less than a factor of two away from being cost competitive and already outperform several other new technologies. Furthermore, we indicate how the performance of the GAP can still be improved by further exploiting its non-equilibrium character. Hence, it is clear that the GAP is very promising for CO2 conversion.

Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C.

Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 99,843 putative new lncRNAs were identified, in which 1220 differentially expressed transcripts exhibited >2-fold change. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. On the basis of a series of filtering pipelines, one lncRNA, TCONS_00075467, was selected to explore its effects and mechanisms on electrical remodeling. The atrial effective refractory period was shortened in vivo and the L-type calcium current and action potential duration were decreased in vitro by silencing of TCONS_00075467 with lentiviruses. Besides, the expression of miRNA-328 was negatively correlated with TCONS_00075467. We further demonstrated that TCONS_00075467 could sponge miRNA-328 in vitro and in vivo to regulate the downstream protein coding gene CACNA1C. In addition, miRNA-328 could partly reverse the effects of TCONS_00075467 on electrical remodeling. In summary, dysregulated lncRNAs may play important roles in modulating electrical remodeling during AF. Our study may facilitate the mechanism studies of lncRNAs in AF pathogenesis and provide potential therapeutic targets for AF.

Nitrogen Fixation by Gliding Arc Plasma: Better Insight by Chemical Kinetics Modelling.

The conversion of atmospheric nitrogen into valuable compounds, that is, so-called nitrogen fixation, is gaining increased interest, owing to the essential role in the nitrogen cycle of the biosphere. Plasma technology, and more specifically gliding arc plasma, has great potential in this area, but little is known about the underlying mechanisms. Therefore, we developed a detailed chemical kinetics model for a pulsed-power gliding-arc reactor operating at atmospheric pressure for nitrogen oxide synthesis. Experiments are performed to validate the model and reasonable agreement is reached between the calculated and measured NO and NO2 yields and the corresponding energy efficiency for NOx formation for different N2 /O2 ratios, indicating that the model can provide a realistic picture of the plasma chemistry. Therefore, we can use the model to investigate the reaction pathways for the formation and loss of NOx . The results indicate that vibrational excitation of N2 in the gliding arc contributes significantly to activating the N2 molecules, and leads to an energy efficient way of NOx production, compared to the thermal process. Based on the underlying chemistry, the model allows us to propose solutions on how to further improve the NOx formation by gliding arc technology. Although the energy efficiency of the gliding-arc-based nitrogen fixation process at the present stage is not comparable to the world-scale Haber-Bosch process, we believe our study helps us to come up with more realistic scenarios of entering a cutting-edge innovation in new business cases for the decentralised production of fertilisers for agriculture, in which low-temperature plasma technology might play an important role.

Association of pre-ablation level of potential blood markers with atrial fibrillation recurrence after catheter ablation: a meta-analysis.

AIMS: The meta-analysis was aimed to search for candidate blood markers whose pre-ablation level was associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). METHODS AND RESULTS: A systematic literature search of PubMed, EMBASE, Springer Link, Web of Science, Wiley-Cochrane library, and supplemented with Google scholar search engine was performed. Thirty-six studies covering 11 blood markers were qualified for this meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased pre-ablation level of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), C-reactive protein, low density lipoprotein (LDL), and tissue inhibitor of metal loproteinase-2 (TIMP-2) [standardized mean difference (95% confidence interval): 0.37 (0.13-0.61), 0.77 (0.40-1.14), 1.25 (0.64-1.87), 0.37 (0.21-0.52), 0.35 (0.10-0.60), 0.24 (0.07-0.42), 0.17 (0.00-0.34), respectively], while no statistical difference of pre-ablation level of white blood cell, total cholesterol, triglyceride, and transforming growth factor-ß1 was found. Subgroup analysis demonstrated that ANP was associated with AF recurrence in participants who had no concomitant structural heart diseases (SHD); however, not in participants who had SHD, C-reactive protein was associated with AF recurrence in Asian studies, whereas not in European studies. CONCLUSION: Increased pre-ablation level of ANP, BNP, NT-pro-BNP, IL-6, C-reactive protein, LDL, and TIMP-2 was associated with greater risk of AF recurrence after RFCA.

Atrial Heterogeneous Autonomic Neural Remodeling in Rabbits with Experimental Atrial Fibrillation and the Effect of Intervention by Rosuvastatin.

BACKGROUND: The study aimed to observe the effects of pacing on the atrial effective refractory period (AERP), inducibility of atrial fibrillation (AF), and changes of atrial autonomic neural remodeling (ANR) by rosuvastatin intervention on the acute model of rapid-pacing-induced AF. METHODS: Thirty rabbits were randomly divided into a control group (C, n = 10), rapid-pacing group (P, n = 10), and rosuvastatin-intervention group (R, n = 10). AERP and inducibility of AF were measured for all groups. The sympathetic and parasympathetic nerves of left atrium, right atrium, and atrial septum labeled with tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) were detected by immunohistochemistry and Western blot. RESULTS: The AERP in group R was prolonged, and AF could not be induced as easily (P < 0.05). Immunohistochemistry showed that the densities and heterogeneity of TH and ChAT positive nerves of the atrium in group P were significantly higher than those in group C (ranked as right atrium > atrial septum > left atrium), whereas those in group R were decreased (P < 0.05). Western blot showed that TH and ChAT protein expression in group P was significantly increased compared with group C, but decreased in group R (P < 0.05). CONCLUSIONS: Persistent rapid atrial pacing can lead to heterogeneous ANR in different parts of the rabbit atrium and may cause AF, which can be reversed by rosuvastatin. The inhibitory function of rosuvastatin may be associated with its role in reversing atrial ANR.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model.

BACKGROUND: The long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues remain unclear. METHODS AND RESULTS: Dogs in group 1 (control, n=8) were not subjected to ganglionated plexi ablation and observed for 1 month, and dogs in groups 2 to 4 (ablation groups, n=8 each) underwent ablation of the right-sided ganglionated plexi and observed for 1, 6, and 12 months, respectively. Atrial electrophysiological characteristics were examined before ablation, immediately and continuously after ablation. Target atrial tissues were subjected to immunohistochemical staining and Western blot analysis. Atrial effective refractory period was significantly prolonged immediately after ablation (P<0.001), and persisted for 1 month (P<0.05). Nerve densities decreased 1 month after ablation (P<0.001). These parameters reverted to preablation levels after 6 and 12 months. In the ablation groups, atrial fibrillation was induced in 5 of 8 dogs after 1 month and in all animals after 6 and 12 months. Atrial fibrillation was not observed in the control group and in the experimental groups immediately after ablation. Moreover, the expression of the growth-associated protein 43 was upregulated after ablation. CONCLUSIONS: Ganglionated plexi ablation effectively prolonged atrial effective refractory period for a short period, but the long-term effects on atrial effective refractory period and the suppression of atrial fibrillation induction were not persistent. Targeted atrial neuron remodeling may be an important mechanism underlying the observed electrophysiological changes.

Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling.

Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be involved in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks. However, little is known about the relationships between lncRNAs and cardiac ANR in AF. In this study, second-generation RNA sequencing was performed to examine the transcriptomes of lncRNAs in AF and non-AF canine cardiac fat pads. A total of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410 were upregulated with more than twofold change. Bioinformatics analysis showed that the aberrantly expressed genes were associated with neural development, migration and neurodegenerative disorders. On the basis of a series of filtering pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo could significantly shorten or prolong the atrial effective refractory period thereby increasing or preventing AF inducibility by promoting or inhibiting the neurogenesis. Besides, the expression of CCND1-FGF19-FGF4-FGF3 gene cluster and SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by increasing the CCND1-FGF19-FGF3-FGF4 gene cluster and SLC25A4 via complex mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may play regulatory roles in AF neural remodeling, which may further provide potential therapeutic targets for prophylaxis and treatment of AF.

Perioperative anticoagulation management in patients on chronic oral anticoagulant therapy undergoing cardiac devices implantation: a meta-analysis.

The perioperative anticoagulation strategy during cardiac implantable electronic devices (CIEDs) implantation is highly variable without consensus among implanting physicians. A systematic literature search was performed in MEDLINE, EMBASE, and the Cochrane Library to identify clinical trials in patients on chronic oral anticoagulant (OAC) therapy undergoing CIEDs implantation. Bleeding and thromboembolic events were compared among heparin bridging, continued OAC, and interrupted OAC groups. Data were expressed as relative risks (RRs) and 95% confidence intervals (CIs) using random effects model. According to the inclusion criteria, totally 14 studies involving 3,744 patients were identified and included in the study. The heparin bridging group showed a significantly higher risk of bleeding events (relative risk [RR] 3.10, 95% confidence interval [CI], 2.02-4.76, P < 0.00001), especially pocket hematoma (RR 3.58, 95% CI, 2.17-5.91, P < 0.00001), but no significantly lower incidence of thromboembolism (RR 1.16, 95% CI, 0.36-3.67, P = 0.81) compared with OAC continuation group. Meanwhile, both unfractionated heparin-bridged and low-molecular-weight heparin-bridged subgroup exhibited a higher risk of bleeding. There was no significant difference between OAC continuation and OAC interruption group in bleeding (RR 0.90, 95% CI, 0.65-1.24, P = 0.52) and thromboembolic (RR 0.57, 95% CI, 0.16-2.01, P = 0.38) complications. The OAC interruption group had an obviously lower incidence of bleeding in comparison with the heparin bridging group and no statistical significance was observed in thrombus occurrence. Implantation of CIEDs with continuous OAC therapy may offer the best option by combining the lower risk of bleeding with rare thromboembolism compared with heparin bridging and OAC interruption therapy.

MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model.

BACKGROUND: The potential mechanisms of microRNA-1 (miR-1) in the electrical remodeling of atrial fibrillation remain unclear. The purpose of this study was to evaluate the effects of miR-1 on the atrial effective refractory period (AERP) in a right atrial tachypacing model and to elucidate the potential mechanisms. METHODS AND RESULTS: QRT-PCR and western blot were used to detect the expression of the miR-1, KCNE1, and KCNB2 genes after 1-week of right atrial tachypacing in New Zealand white rabbits. The AERP was measured using a programmable multichannel stimulator, and atrial fibrillation was induced by burst stimulation in vivo. The slowly activating delayed rectifier potassium current (IKs) and AERP in atrial cells were measured by whole cell patch clamp in vitro. Right atrial tachypacing upregulated miR-1 expression and downregulated KCNE1 and KCNB2 in this study, while the AERP was decreased and the atrial IKs increased. The downregulation of KCNE1 and KCNB2 levels was greater when miR-1 was further upregulated through in vivo lentiviral infection. Electrophysiological tests indicated a shorter AERP, a great increase in the IKs and a higher atrial fibrillation inducibility. In addition, similar results were found when the levels of KCNE1 and KCNB2 were downregulated by small interfering RNA while keeping miR-1 level unaltered. Conversely, knockdown of miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs. KCNE1 and KCNB2 as the target genes for miR-1 were confirmed by luciferase activity assay. CONCLUSIONS: These results indicate that miR-1 accelerates right atrial tachypacing-induced AERP shortening by targeting potassium channel genes, which further suggests that miR-1 plays an important role in the electrical remodeling of atrial fibrillation and exhibits significant clinical relevance as a potential therapeutic target for atrial fibrillation.