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BACKGROUND: The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of KCa3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing. METHODS: Part 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were cocultured to explore the specific migratory mechanism of macrophages. RESULTS: Depleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodeling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells were significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that KCa3.1 regulated CCL2 secretion through the p65/STAT3 signaling pathway. CONCLUSION: Inhibiting myocardial KCa3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which KCa3.1 regulates CCL2 may be related to the p65/STAT3 signaling pathway.
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Background: Fibroblast-derived exosomes can regulate the electrical remodeling of cardiomyocytes, and the intermediate-conductance calcium-activated potassium channel (KCa3.1) is important in atrial electrical remodeling. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the regulation of cardiac electrophysiology by exosomes linked to KCa3.1. Methods: Atrial myocytes (AMs) and atrial fibroblasts were isolated from Sprague-Dawley suckling rats and cultured individually. The cellular atrial fibrillation (AF) model was established via electrical stimulation (1.0 v/cm, 10 Hz), and fibroblast-derived exosomes were isolated via ultracentrifugation. Exosomes were co-cultured with AMs to investigate their influences on KCa3.1 and the underlying mechanisms. Nanoparticle tracking analysis and transmission electron microscopy were used to measure exosome particle sizes and concentrations. Whole-cell patch clamp was applied to record the current density of KCa3.1 and action potential duration (APD). The expression of miR-21-5p was detected by reverse-transcription polymerase chain reaction (RT-PCR). Western blotting or immunofluorescence was used to measure the expression of exosomal markers, Akt phosphorylation, and KCa3.1. Results: Rapid pacing promoted the secretion of exosomes from atrial fibroblasts and miR-21-5p expression in atrial fibroblasts and exosomes. KCa3.1 protein expression and current density significantly increased, and APD50 and APD90 were sharply shortened after rapid pacing in AMs. TRAM-34 (KCa3.1 blocker) extended APD and reduced susceptibility to AF. KCa3.1 and P-AKT expressions were amplified after co-culturing AMs with exosomes secreted by atrial fibroblasts. In contrast, the increase in KCa3.1 expression was reversed after the cells were co-cultured with exosomes secreted by atrial fibroblasts that were transfected with miR-21-5p inhibitors or after the use of LY294002, a PI3K/Akt pathway inhibitor. Conclusions: Rapid pacing promoted the secretion of exosomes from fibroblasts, and miR-21-5p was upregulated in exosomes. Moreover, the miR-21-5p-enriched exosomes upregulated KCa3.1 expression in AMs via the PI3K/Akt pathway.
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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.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco , China/epidemiologia , PrevalênciaRESUMO
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.
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Fibrilação Atrial , Exossomos , MicroRNAs , Prolina , Tiocarbamatos , Humanos , Fibrilação Atrial/metabolismo , Estimulação Cardíaca Artificial , Exossomos/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Prolina/análogos & derivados , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Animais , Camundongos , Linhagem CelularRESUMO
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.
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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.