Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.

M2 macrophage­derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL­1 myocytes via the NF­κB (p65)/STAT3 signaling pathway.

The present study was designed to explore the role of M2 macrophage­derived exosomes (M2­exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL­1 myocytes. M2 macrophages and M2­exos were isolated and identified. MicroRNA (miR)­146a­5p levels in M2 macrophages and M2­exos were quantified using reverse transcription­quantitative PCR (RT­qPCR). HL­1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL­1 cells cocultured with M2­exos), pacing + mimic­miR­146a­5p group, pacing + NC­miR­146a­5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF­κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT­qPCR and immunohistochemistry were performed in the present study. A whole­cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR­146a­5p was highly expressed in both M2 macrophages and M2­exos. Pacing HL­1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p­)NF­κB p65, p­STAT3 and IL­1ß compared with the control group. M2­exos, miR­146a­5p­mimic and PDTC both reduced the protein expression of KCa3.1, p­NF­κB p65, p­STAT3 and IL­1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL­1 cells. In conclusion, M2­exos and their cargo, which comprised miR­146a­5p, decreased KCa3.1 expression and IL­1ß secretion in pacing HL­1 cells via the NF­κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

Macrophage colony-stimulating factor ameliorates myocardial injury in mice after myocardial infarction by regulating cardiac macrophages through the P2X7R/NLRP3/IL-1ß signal pathway.

Aims: To investigate the effects of M-CSF on myocardial injury in mice after MI by regulating different types of cardiac macrophages through the P2X7R/NLRP3/IL-1ß signal pathway. Methods: A total of 60 C57BL/6J WT mice were used, with the Sham Group subjected to ligation without ligation through the LAD, the MI model was prepared by ligation of the LAD in the MC Group and MM Group, with the M-CSF reagent (500 µg/kg/d) being given an intraperitoneal injection for the first 5 days after surgery in the MM Group. All mice were fed in a barrier environment for 1 week. After the study, myocardial tissues were collected and IL-4, IL-6, IL-10, TNF-α, MCP-1, IFN-α, ANP, BNP, ß-MHC, Collage I, Collage III, P2X7R, NLRP3, IL-1ß, Bax, Caspase 3, C-Casp 3, Bcl-2, M1/2 macrophage, the apoptosis of cardiomyocytes, and the collagen deposition were detected. Results: The inflammatory response was significantly lower in the MM Group, the cardiomyocyte apoptosis, fibrosis, and hypertrophy were inhibited compared to the MC Group, and the levels of P2X7R, NLRP3, and IL-1ß were also statistically lower in the MM Group. Additionally, the expression of M2 macrophages increased in the MM Group while the M1 macrophages statistically decreased compared to the MC Group. Conclusion: M-CSF can significantly increase the expression of M2 macrophage and reduce the level of M1 macrophage by inhibiting the levels of NLRP3/IL-1ß-related proteins, thereby inhibiting inflammation, ameliorating reducing myocardial hypertrophy, apoptosis, and fibrosis, improve myocardial injury in mice after MI.

Comprehensive Optimization of Western Blotting.

Western blotting is one of the most extensively used techniques in the biomedical field. However, it is criticized by many researchers due to its considerable time consumption, multiple steps, and low method results. Therefore, we modified the steps of gel preparation, electrophoresis, electrotransfer, blocking, and gel cutting. First, we simplified the gel preparation step by premixing various reagents and varying the amounts of catalysts or radical generators, which shortened the entire process to 10 min. Second, we shortened the electrophoresis process to 35 min by modifying the formula of the electrophoresis running buffer. Then, we removed the hazard of methanol vapor by replacing methanol with ethanol in the electrotransfer buffer. Finally, the use of polyvinylpyrrolidone-40 shortened the blocking procedure to 10 min. Our modifications shortened the time, improved the experimental productivity, and minimized the experimental cost without hindering compatibility with most existing equipment. The entire experiment up to primary antibody incubation can be completed within 80 min.

Effects of Inflammatory Cell Death Caused by Catheter Ablation on Atrial Fibrillation.

Atrial fibrillation (AF) poses a serious healthcare burden on society due to its high morbidity and the resulting serious complications such as thrombosis and heart failure. The principle of catheter ablation is to achieve electrical isolation by linear destruction of cardiac tissue, which makes AF a curable disease. Currently, catheter ablation does not have a high long-term success rate. The current academic consensus is that inflammation and fibrosis are central mechanisms in the progression of AF. However, artificially caused inflammatory cell death by catheter ablation may have a significant impact on structural and electrical remodeling, which may affect the long-term prognosis. This review first focused on the inflammatory response induced by apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis and their interaction with arrhythmia. Then, we compared the differences in cell death induced by radiofrequency ablation, cryoballoon ablation and pulsed-field ablation. Finally, we discussed the structural and electrical remodeling caused by inflammation and the association between inflammation and the recurrence of AF after catheter ablation. Collectively, pulsed-field ablation will be a revolutionary innovation with faster, safer, better tissue selectivity and less inflammatory response induced by apoptosis-dominated cell death.

Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC-MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45-807.43) and 484.22 (311.91-626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Advances in basic and translational research in atrial fibrillation.

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

KCa3.1 Promotes Proinflammatory Exosome Secretion by Activating AKT/Rab27a in Atrial Myocytes during Rapid Pacing.

Purpose: The aim of this study was to investigate the role of the medium-conductance calcium-activated potassium channel (KCNN4, KCa3.1) in the secretion of proinflammatory exosomes by atrial myocytes. Methods: Eighteen beagles were randomly divided into the sham group (n = 6), pacing group (n = 6), and pacing+TRAM-34 group (n = 6). Electrophysiological data, such as the effective refractory period, atrial fibrillation (AF) induction, and AF duration, were collected by programmed stimulation. Atrial tissues were subjected to hematoxylin and eosin, Masson's trichrome, and immunofluorescence staining. The expression of KCa3.1 and Rab27a was assessed by immunohistochemistry and western blotting. The downstream signaling pathways involved in KCa3.1 were examined by rapid pacing or overexpressing KCNN4 in HL-1 cells. Results: Atrial rapid pacing significantly induced electrical remodeling, inflammation, fibrosis, and exosome secretion in the canine atrium, while TRAM-34 (KCa3.1 blocker) inhibited these changes. Compared with those in control HL-1 cells, the levels of exosome markers and inflammatory factors were increased in pacing HL-1 cells. Furthermore, the levels of CD68 and iNOS in macrophages incubated with exosomes derived from HL-1 cells were higher in the pacing-exo group than in the control group. More importantly, KCa3.1 regulated exosome secretion through the AKT/Rab27a signaling pathway. Similarly, inhibiting the downstream signaling pathway of KCa3.1 significantly inhibited exosome secretion. Conclusions: KCa3.1 promotes proinflammatory exosome secretion through the AKT/Rab27a signaling pathway. Inhibiting the KCa3.1/AKT/Rab27a signaling pathway reduces myocardial tissue structural remodeling in AF.

Inhibition of intermittent calcium-activated potassium channel (SK4) attenuates Ang II-induced hypertrophy of human-induced stem cell-derived cardiomyocytes via targeting Ras-Raf-MEK1/2-ERK1/2 and CN-NFAT signaling pathways.

Cardiac hypertrophy caused by angiotensin II (Ang II) is essential for the pathological process of heart failure. The intermediate calcium-activated potassium channel (SK4) has been shown to be involved in the process of the inflammatory response, cell proliferation, and apoptosis. However, the role of SK4 in cardiac hypertrophy has not been elucidated. Cardiac hypertrophy in human-induced pluripotent stem cells-derived cardiomyocytes (HiPSC-CMs) was induced by Ang II. Cells were transfected with SK4 adenovirus or treated with SK4 inhibitor (TRAM-34). TUNEL staining was used to assess the levels of apoptosis. Real-time polymerase chain reaction and Western blot analysis were used to measure messenger RNA (mRNA) and protein levels, respectively. The present results showed that SK4 expression was upregulated in HiPSC-CMs stimulated by Ang II. The downregulation of SK4 by a specific inhibitor TRAM-34 markedly ameliorated cardiac hypertrophy (reflected by the mRNA levels of atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain) and apoptosis (reflected by the level of Caspase 3, Bax, and Bcl-2) induced by Ang II treatment. The action of SK4 in cardiac hypertrophy was mediated by Ras-Raf-mitogen-activated protein kinases 1/2 (MEK1/2)-extracellular-regulated protein kinases 1/2 (ERK1/2) and calcineurin (CN)-nuclear factors of activated T cells (NFAT) activation. Our studies demonstrated that inhibition of SK4 significantly alleviated cardiac hypertrophy induced by Ang II in hiPSC-CMs by targeting Ras-Raf-MEK1/2-ERK1/2 signaling and CN-NFAT signaling pathway. Our studies suggest that SK4 may serve as a potential therapeutic target that could delay hypertrophy.

The genus Eurymeros Bhat (Hymenoptera, Braconidae, Alysiinae) newly recorded from China.

Background: Alysiinae Leach is a species-rich subfamily in Braconidae, of which several species play an important role in biological control. The monotypic genus Eurymerostumespiraculum Bhat, 1980 was discovered in Tibet and Yunnan provinces for the first time, representing the first record of the genus Eurymeros Bhat, 1980 (Braconidae, Alysiinae) in China. New information: The rare genus Eurymeros Bhat, 1980 (Braconidae, Alysiinae) and its only known species, E.tumespiraculum Bhat, 1980, are newly recorded from China. The morphological variation of the Chinese specimens is described and illustrated.

A new species of the genus Wushenia Zettel, 1990 from China (Hymenoptera: Braconidae: Cheloninae).

Wushenia Zettel, 1990 is a rare genus (with the type species Wushenia nana Zettel) first collected in Wushe (Taiwan) in 1983. Here we describe a second species, Wushenia yekunzengi Yao & Luo sp. nov., from Gaoligong Mountain Nature Reserve, Yunnan and Emei Mountain, Sichuan, China. A key to species of the genus Wushenia is presented. In addition, Wushenia australiensis Kittel & Austin, 2013 is excluded from the genus Wushenia Zettel.

Blockade of SK4 channels suppresses atrial fibrillation by attenuating atrial fibrosis in canines with prolonged atrial pacing.

Background: We previously found that intermediate conductance Ca2+-activated K+ channel (SK4) might be an important target in atrial fibrillation (AF). Objective: To investigate the role of SK4 in AF maintenance. Methods: Twenty beagles were randomly assigned to the sham group (n=6), pacing group (n=7), and pacing+TRAM-34 group (n=7). Rapid atrial pacing continued for 7 days in the pacing and TRAM-34 groups. During the pacing, the TRAM-34 group received TRAM-34 intravenous injection (10 mg/Kg) 3 times per day. Atrial fibroblasts isolated from canines were treated with angiotensin II or adenovirus carrying the SK4 gene (Ad-SK4) to overexpress SK4 channels. Results: TRAM-34 treatment significantly suppressed the increased intra-atrial conducting time (CT) and AF duration in canines after rapid atrial pacing (P<0.05). Compared with the sham group, the expression of SK4 in atria was higher in the pacing group, which was associated with an increased number of myofibroblasts and levels of extracellular matrix in atrium (all P<0.05), and this effect was reversed by TRAM-34 treatment (all P<0.05). In atrial fibroblasts, the increased expression of SK4 induced by angiotensin II stimulation or Ad-SK4 transfection contributed to higher levels of P38, ERK1/2 and their downstream factors c-Jun and c-Fos, leading to the increased expression of α-SMA (all P<0.05), and all these increases were markedly reduced by TRAM-34 treatment. Conclusion: SK4 blockade suppressed AF by attenuating cardiac fibroblast activity and atrial fibrosis, which was realized through not only a decrease in fibrogenic factors but also inhibition of fibrotic signaling pathways.

Median nerve stimulation elevates ventricular fibrillation threshold via the cholinergic anti-inflammatory pathway in myocardial infarction canine model.

Background: Median nerve stimulation (MNS) diminishes regional myocardial ischemia and ventricular arrhythmia; however, the underlying mechanism has not been elucidated. Methods: In this study, we randomly categorized 22 adult mongrel dogs into a control group, MNS group 1, and MNS group 2. After a 4-week experimental myocardial infarction (MI), ventricular electrophysiology was measured in the MNS group 1 before and after 30 min of MNS. The same measurements were performed in the MNS group 2 dogs via bilateral vagotomy. Venous blood and ventricular tissue were collected to detect molecular indicators related to inflammation and cholinergic pathways by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and Western blot (WB). Results: No significant changes were reported in the ventricular effective refractory period (ERP) in the MNS group 1 and MNS group 2 dogs before and after MNS. The ventricular fibrillation threshold (VFT) in the MNS group 1 was significantly higher than that in the MNS group 2 (20.3 ± 3.7 V vs. 8.7 ± 2.9 V, P < 0.01). The levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear transcription factor-κB (NF-κB) were lower (P < 0.01), whereas the levels of Ach were higher in the peri-infarct zone tissues in the MNS group 1 dogs than those in the MNS group 2 dogs (P < 0.01). Conclusion: This study demonstrated that MNS increases VFT in a canine model with MI. The effects of MNS on VFT are potentially associated with the cholinergic anti-inflammatory pathway.

Immune remodeling and atrial fibrillation.

Atrial fibrillation (AF) is a highly prevalent arrhythmia that causes high morbidity and mortality. However, the underlying mechanism of AF has not been fully elucidated. Recent research has suggested that, during AF, the immune system changes considerably and interacts with the environment and cells involved in the initiation and maintenance of AF. This may provide a new direction for research and therapeutic strategies for AF. In this review, we elaborate the concept of immune remodeling based on available data in AF. Then, we highlight the complex relationships between immune remodeling and atrial electrical, structural and neural remodeling while also pointing out some research gaps in these field. Finally, we discuss several potential immunomodulatory treatments for AF. Although the heterogeneity of existing evidence makes it ambiguous to extrapolate immunomodulatory treatments for AF into the clinical practice, immune remodeling is still an evolving concept in AF pathophysiology and further studies within this field are likely to provide effective therapies for AF.

Dapagliflozin Protects Methamphetamine-Induced Cardiomyopathy by Alleviating Mitochondrial Damage and Reducing Cardiac Function Decline in a Mouse Model.

Background: Methamphetamine (METH)-induced cardiovascular toxicity has been attributed to its destructive effect on mitochondrial function at least to some extent. Previous studies highlighted the benefits of dapagliflozin (DAPA) on the cardiovascular system, but the response of METH-induced cardiomyopathy to DAPA is never addressed before. The present study aimed to investigate the potential ability of DAPA in preventing METH-induced cardiomyopathy. Materials and Methods: C57BL/6 mice were randomly divided into control group (n = 24), METH group (n = 24), and METH + DAPA group (n = 24). The METH-induced cardiomyopathy group received intraperitoneal METH injections at gradually increasing doses thrice weekly for 14 weeks. Mice in the METH + DAPA group were simultaneously treated with DAPA 1 mg/kg/day by intragastric administration. Echocardiography was performed to assess cardiac function. Reactive oxygen species (ROS), JC-1, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were performed to evaluate oxidative stress, mitochondrial damage, and apoptosis, respectively. Mitochondrial and apoptosis-related protein expression was measured by western blotting. Results: Mice exposed to METH exhibited reduced cardiac function (left ventricular ejection fraction [LVEF]: 56.51 ± 6.49 vs. 73.62 ± 1.42, p < 0.01), fibrotic remodeling, and mitochondrial dysfunction, leading to apoptosis (apoptotic cells%: 7.4 ± 1.3 vs. 1.3 ± 0.5, p < 0.01). DAPA significantly reduced mitochondrial dynamics and function, ROS, apoptosis (apoptotic cells%: 2.4 ± 0.8 vs. 7.4 ± 1.3, p < 0.01), cardiac function decline (LVEF: 70.99 ± 4.936 vs. 56.51 ± 6.49, p < 0.01), and fibrotic remodeling. These results indicated that DAPA could be considered as an effective therapeutic agent in the protection against METH-associated cardiomyopathy. Conclusion: DAPA protects against METH-induced cardiomyopathy in mice by decreasing mitochondrial damage and apoptosis.

Sinapic Acid Attenuated Cardiac Remodeling After Myocardial Infarction by Promoting Macrophage M2 Polarization Through the PPARγ Pathway.

Background: Macrophage polarization is an important regulatory mechanism of ventricular remodeling. Studies have shown that sinapic acid (SA) exerts an anti-inflammatory effect. However, the effect of SA on macrophages is still unclear. Objectives: The purpose of the study was to investigate the role of SA in macrophage polarization and ventricular remodeling after myocardial infarction (MI). Methods: An MI model was established by ligating the left coronary artery. The rats with MI were treated with SA for 1 or 4 weeks after MI. The effect of SA on bone marrow-derived macrophages (BMDMs) was also observed in vitro. Results: Cardiac systolic dysfunction was significantly improved after SA treatment. SA reduced MCP-1 and CCR2 expression and macrophage infiltration. SA decreased the levels of the inflammatory factors TNF-α, IL-1α, IL-1ß, and iNOS and increased the levels of the M2 macrophage markers CD206, Arg-1, IL-10, Ym-1, Fizz-1, and TGF-ß at 1 week after MI. SA significantly increased CD68+/CD206+ macrophage infiltration. Myocardial interstitial fibrosis and MMP-2 and MMP-9 levels were decreased, and the sympathetic nerve marker TH and nerve sprouting marker GAP43 were suppressed after SA treatment at 4 weeks after MI. The PPARγ level was notably upregulated after SA treatment. In vitro, SA also increased the expression of PPARγ mRNA in BMDMs and IL-4-treated BMDMs in a concentration-dependent manner. SA enhanced Arg1 and IL-10 expression in BMDMs, and the PPARγ antagonist GW9662 attenuated M2 macrophage marker expression. Conclusions: Our results demonstrated that SA attenuated structural and neural remodeling by promoting macrophage M2 polarization via PPARγ activation after MI.

Prevalence and risk of atrial fibrillation in China: A national cross-sectional epidemiological study.

Background: Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China. Methods: Study data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results. Findings: A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval [CI] 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 [95% CI 1·38-1·46]; p < 0·001), men (1·34 [1·24-1·45]; p < 0·001), hypertension (1·22 [1·12-1·33]; p < 0·001), coronary heart disease (1·44 [1·28-1·62]; p < 0·001), chronic heart failure (3·70 [3·22-4·26]; p < 0·001), valvular heart disease (2·13 [1·72-2·63]; p < 0·001), and transient ischaemic attack/stroke (1·22 [1·04-1·43]; p = 0·013). Interpretation: The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden. Funding: This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).

Pinocembrin Decreases Atrial Fibrillation Susceptibility in a Rodent Model of Depression.

Background: Depression is often comorbid with cardiovascular diseases and contributes to the development and maintenance of atrial fibrillation (AF). Ample research demonstrated that pinocembrin had protective effects on the neuropsychiatric and cardiovascular systems via its pharmacological properties. However, whether pinocembrin protects from AF in depression models is not known. The present research investigated antiarrhythmic effects of pinocembrin and the underlying mechanisms in depressed rats. Methods: One hundred and ten male Sprague Dawley rats were randomly divided into six groups: the CTL group (the normal rats administered saline), the CTP group (the normal rats administered pinocembrin), the MDD group (the depressed rats administered saline), the MDP group (the depressed rats administered pinocembrin), the MDA group (the depressed rats administered apocynin), and the MPA group (the depressed rats administered both pinocembrin and apocynin). Chronic unpredictable mild stress (CUMS) was performed for 28 days to establish the depression model. Pinocembrin was administered via gavage from Day 8 to Day 28, and apocynin was administered via intraperitoneal injection from Day 1 to Day 28. The effects were evaluated using behavioral measurements, in vitro electrophysiological studies, whole-cell patch-clamp recordings, biochemical detection, Western blot, and histological studies. Results: Pinocembrin treatment significantly attenuated the abnormality of heart rate variability (HRV), the prolongation of action potential duration (APD), the shortening of the effective refractory period (ERP), the reduction of transient outward potassium current (Ito), and the increase in L-type calcium current (ICa-L), which increase susceptibility to AF in a rat model of depression. Compared to the depressed rats, pinocembrin also increased the content of Kv4.2, Kv4.3, and atrial gap junction channel Cx40 and decreased the expression level of Cav1.2, which ameliorated oxidative stress and inhibited the ROS/p-p38MAPK pro-apoptotic pathway and the ROS/TGF-ß1 pro-fibrotic pathway. Conclusion: Pinocembrin is a therapeutic strategy with great promise for the treatment of AF in depressed patients by reducing oxidative stress.

Cardiac Fibroblasts Promote Ferroptosis in Atrial Fibrillation by Secreting Exo-miR-23a-3p Targeting SLC7A11.

The exact mechanism of atrial fibrillation (AF) has been not well elucidated. Ferroptosis is an iron-dependent cell death due to excessive accumulation of peroxidized polyunsaturated fatty acids. However, the molecular mechanism underlying AF and ferroptosis has never been reported. Here, we established the rapid pacing model in vivo and vitro to investigate the relationship between AF and ferroptosis. In canine model of rapid atrial pacing, the content of malondialdehyde and total ions in the atrial tissue of the Pacing group was significantly increased and the exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. In rapid pacing h9c2 cells, the expression of antioxidative stress genes associated with ferroptosis presented sequential changes and proteins involved in ferroptosis such as FTH1, SLC7A11, and GPX4 were gradually depleted. Furthermore, pacing cardiac fibroblast-derived exosomes (CF-exos) exacerbated ferroptosis in h9c2 cells and pretreated pacing-CF-exos with GW4869 alleviated injury to h9c2 cells. In mechanism, our results demonstrated that pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor-miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. In addition, SLC7A11 was shown to be the target gene of miR-23a-3p. In conclusion, our results suggest that CF-exos-miR-23a-3p may promote ferroptosis. The development of AF in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis.

Left Atrial Thrombus in Patients With Non-valvular Atrial Fibrillation: A Cross-Sectional Study in China.

Background: Stroke is predominately attributed to left atrial thrombus (LAT) in patients with non-valvular atrial fibrillation (NVAF), however, its detection rate in real clinical practice has been few reported in China. Objective: This study aimed to investigate the prevalence and associated factors of LAT in patients with NVAF in China. Methods: All adult NVAF patients undergoing transesophageal echocardiography (TEE) in the China Atrial Fibrillation Center database from January 2017 to January 2022 were enrolled in this study. The prevalence of LAT was calculated, and associated factors were identified. Results: A total of 36,007 NVAF inpatients from 602 hospitals in 30 provinces/autonomous regions/municipalities were included in the final analysis, with a median age of 66 years and 39.4% were female. LAT was present in 1,467 (4.1%) patients overall, 2.7, 5.7, and 6.8% in patients with paroxysmal, persistent, and long-standing persistent AF, respectively. In subgroup analysis, including age ≥ 65 years, CHA2DS2-VASC score ≥ 2, left atrial diameter (LAD) ≥ 50 mm, left ventricular ejection fraction (LVEF) < 50%, and anticoagulation, patients with paroxysmal AF always had the lowest LAT prevalence, followed by patients with persistent and long-standing persistent AF. Patients treated with anticoagulants had less prevalent LAT than those without anticoagulation (2.1 vs. 5.0%, p < 0.001). In multivariate analysis, AF pattern (both persistent AF and long-standing persistent AF), hypertension, chronic heart failure, coronary heart disease, transient ischemic attack/stroke, diabetes mellitus, and LAD (per 5 mm) were associated with an increased prevalence of LAT. However, LVEF (per 5%) and anticoagulation were associated with a reduced prevalence of LAT. Conclusion: LAT was found in 4.1% of Chinese adult NVAF inpatients underwent TEE in real-world experience. The prevalence of LAT mainly associated with non-paroxysmal AF, cardiovascular diseases, diabetes mellitus, enlarged left atrium, lower LVEF, and lack of anticoagulation therapy.