{"title":"牙龈卟啉单胞菌心房易位加重心房纤维化和心房颤动。","authors":"Shunsuke Miyauchi, Miki Kawada-Matsuo, Hisako Furusho, Hiromi Nishi, Ayako Nakajima, Pham Trong Phat, Fumie Shiba, Masae Kitagawa, Kazuhisa Ouhara, Noboru Oda, Takehito Tokuyama, Yousaku Okubo, Sho Okamura, Taiichi Takasaki, Shinya Takahashi, Toru Hiyama, Hiroyuki Kawaguchi, Hitoshi Komatsuzawa, Mutsumi Miyauchi, Yukiko Nakano","doi":"10.1161/CIRCULATIONAHA.124.071310","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. <i>Porphyromonas gingivalis (P ginigivalis</i>) is a causative agent of periodontal disease and is highly pathogenic. This study focused on <i>P</i> <i>gingivalis</i> and aimed to investigate the relationship among periodontitis, atrial translocation of <i>P</i> <i>gingivalis</i>, and atrial fibrosis and AF.</p><p><strong>Methods: </strong>An experiment was conducted using <i>P</i> <i>gingivalis</i>-infected C57BL/6J mice, in which <i>P</i> <i>gingivalis</i> was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of <i>P</i> <i>gingivalis</i>, and loop-mediated isothermal amplification was employed to detect <i>P</i> <i>gingivalis</i> DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of <i>P</i> <i>gingivalis</i> in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining.</p><p><strong>Results: </strong>The translocation path of <i>P</i> <i>gingivalis</i> from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in <i>P</i> <i>gingivalis</i>-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; <i>P</i>=0.0003) and a higher AF inducibility (30.0% versus 5.0%; <i>P</i>=0.04) than the control mice. Upregulation of galectin-3 and transforming growth factor-beta 1 in the left atrium was observed in <i>P</i> <i>gingivalis</i>-infected mice. Moreover, immunohistochemistry revealed that <i>P</i> <i>gingivalis</i> was also present in human atrial tissue. The number of <i>P</i> <i>gingivalis</i> in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; <i>P</i>=0.004), periodontal inflamed surface area (ρ=0.52, <i>P</i><0.0001), and the degree of atrial fibrosis (ρ=0.38; <i>P</i>=0.002).</p><p><strong>Conclusions: </strong><i>P</i> <i>gingivalis</i> translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of <i>P</i> <i>gingivalis</i> is a potential pathway explaining the causal relationship between periodontitis and AF.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1527-1540"},"PeriodicalIF":35.5000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Atrial Translocation of <i>Porphyromonas gingivalis</i> Exacerbates Atrial Fibrosis and Atrial Fibrillation.\",\"authors\":\"Shunsuke Miyauchi, Miki Kawada-Matsuo, Hisako Furusho, Hiromi Nishi, Ayako Nakajima, Pham Trong Phat, Fumie Shiba, Masae Kitagawa, Kazuhisa Ouhara, Noboru Oda, Takehito Tokuyama, Yousaku Okubo, Sho Okamura, Taiichi Takasaki, Shinya Takahashi, Toru Hiyama, Hiroyuki Kawaguchi, Hitoshi Komatsuzawa, Mutsumi Miyauchi, Yukiko Nakano\",\"doi\":\"10.1161/CIRCULATIONAHA.124.071310\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. <i>Porphyromonas gingivalis (P ginigivalis</i>) is a causative agent of periodontal disease and is highly pathogenic. This study focused on <i>P</i> <i>gingivalis</i> and aimed to investigate the relationship among periodontitis, atrial translocation of <i>P</i> <i>gingivalis</i>, and atrial fibrosis and AF.</p><p><strong>Methods: </strong>An experiment was conducted using <i>P</i> <i>gingivalis</i>-infected C57BL/6J mice, in which <i>P</i> <i>gingivalis</i> was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of <i>P</i> <i>gingivalis</i>, and loop-mediated isothermal amplification was employed to detect <i>P</i> <i>gingivalis</i> DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of <i>P</i> <i>gingivalis</i> in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining.</p><p><strong>Results: </strong>The translocation path of <i>P</i> <i>gingivalis</i> from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in <i>P</i> <i>gingivalis</i>-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; <i>P</i>=0.0003) and a higher AF inducibility (30.0% versus 5.0%; <i>P</i>=0.04) than the control mice. Upregulation of galectin-3 and transforming growth factor-beta 1 in the left atrium was observed in <i>P</i> <i>gingivalis</i>-infected mice. Moreover, immunohistochemistry revealed that <i>P</i> <i>gingivalis</i> was also present in human atrial tissue. The number of <i>P</i> <i>gingivalis</i> in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; <i>P</i>=0.004), periodontal inflamed surface area (ρ=0.52, <i>P</i><0.0001), and the degree of atrial fibrosis (ρ=0.38; <i>P</i>=0.002).</p><p><strong>Conclusions: </strong><i>P</i> <i>gingivalis</i> translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of <i>P</i> <i>gingivalis</i> is a potential pathway explaining the causal relationship between periodontitis and AF.</p>\",\"PeriodicalId\":10331,\"journal\":{\"name\":\"Circulation\",\"volume\":\" \",\"pages\":\"1527-1540\"},\"PeriodicalIF\":35.5000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCULATIONAHA.124.071310\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCULATIONAHA.124.071310","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景:最近的研究表明牙周炎和心房颤动(AF)之间存在关联,尽管潜在的机制尚不清楚。牙龈卟啉单胞菌是牙周病的病原体,具有很高的致病性。本研究以牙周炎为研究对象,探讨牙周炎、牙周炎心房易位、心房纤维化与房颤的关系。方法:采用感染牙周炎的C57BL/6J小鼠,在磨牙牙髓中接种牙周炎。免疫组化观察牙龈P的定位,环介导等温扩增检测左心房牙龈P DNA。心内刺激检查心房颤动诱导。68例房颤患者取左心房附件标本,术前行牙周检查,测量牙周上皮表面积和牙周炎症表面积,这是判断牙周炎临床严重程度的定量指标。采用定量聚合酶链反应法对人心房组织中牙龈P菌数量进行了分析。Azan-Mallory染色评估心房纤维化。结果:免疫组织化学和环介导的等温扩增显示牙龈卟啉卟啉感染小鼠的心房纤维化程度较高(21.9%比16.3%;P=0.0003)和更高的AF诱导率(30.0% vs 5.0%;P=0.04)。P龈感染小鼠左心房GAL3(凝集素3)和转化生长因子- β 1表达上调。免疫组化结果显示,牙龈卟啉杆菌也存在于人心房组织中。人心房组织中P龈数与牙周上皮表面积呈正相关(ρ=0.35;P=0.004)、牙周炎症表面积(P= 0.52, PP=0.002)。结论:龈P易位至左心房与牙周炎的临床严重程度相关,可能加重心房纤维化和房颤,龈P心房易位是解释牙周炎与房颤因果关系的一个潜在途径。
Atrial Translocation of Porphyromonas gingivalis Exacerbates Atrial Fibrosis and Atrial Fibrillation.
Background: Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. Porphyromonas gingivalis (P ginigivalis) is a causative agent of periodontal disease and is highly pathogenic. This study focused on Pgingivalis and aimed to investigate the relationship among periodontitis, atrial translocation of Pgingivalis, and atrial fibrosis and AF.
Methods: An experiment was conducted using Pgingivalis-infected C57BL/6J mice, in which Pgingivalis was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of Pgingivalis, and loop-mediated isothermal amplification was employed to detect Pgingivalis DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of Pgingivalis in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining.
Results: The translocation path of Pgingivalis from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in Pgingivalis-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; P=0.0003) and a higher AF inducibility (30.0% versus 5.0%; P=0.04) than the control mice. Upregulation of galectin-3 and transforming growth factor-beta 1 in the left atrium was observed in Pgingivalis-infected mice. Moreover, immunohistochemistry revealed that Pgingivalis was also present in human atrial tissue. The number of Pgingivalis in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; P=0.004), periodontal inflamed surface area (ρ=0.52, P<0.0001), and the degree of atrial fibrosis (ρ=0.38; P=0.002).
Conclusions: Pgingivalis translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of Pgingivalis is a potential pathway explaining the causal relationship between periodontitis and AF.
期刊介绍:
Circulation is a platform that publishes a diverse range of content related to cardiovascular health and disease. This includes original research manuscripts, review articles, and other contributions spanning observational studies, clinical trials, epidemiology, health services, outcomes studies, and advancements in basic and translational research. The journal serves as a vital resource for professionals and researchers in the field of cardiovascular health, providing a comprehensive platform for disseminating knowledge and fostering advancements in the understanding and management of cardiovascular issues.