{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:29:53Z","timestamp":1792175393359,"version":"4.4.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,8,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Systemic inflammation is a strong predictor of atrial fibrillation. A key role for electrical remodeling is increasingly recognized, and experimental data suggest that inflammatory cytokines can directly affect connexins resulting in gap\u2010junction dysfunction. We hypothesized that systemic inflammation, regardless of its origin, promotes atrial electric remodeling in\u00a0vivo, as a result of cytokine\u2010mediated changes in connexin expression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Fifty\u2010four patients with different inflammatory diseases and elevated C\u2010reactive protein were prospectively enrolled, and electrocardiographic P\u2010wave dispersion indices, cytokine levels (interleukin\u20106, tumor necrosis factor\u2010\u03b1, interleukin\u20101, interleukin\u201010), and connexin expression (connexin 40, connexin 43) were measured during active disease and after reducing C\u2010reactive protein by &gt;75%. Moreover, peripheral blood mononuclear cells and atrial tissue specimens from an additional sample of 12 patients undergoing cardiac surgery were evaluated for atrial and circulating mRNA levels of connexins. Finally, in\u00a0vitro effects of interleukin\u20106 on connexin expression were studied in HL\u20101 mouse atrial myocytes. In patients with active inflammatory diseases, P\u2010wave dispersion indices were increased but rapidly decreased within days when C\u2010reactive protein normalizes and interleukin\u20106 levels decline. In inflammatory disease patients, both P\u2010wave dispersion indices and interleukin\u20106 changes were inversely associated with circulating connexin levels, and a positive correlation between connexin expression in peripheral blood mononuclear cells and atrial tissue was demonstrated. Moreover, interleukin\u20106 significantly reduced connexin expression in HL\u20101 cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data suggest that regardless of specific etiology and organ localization, systemic inflammation, via interleukin\u20106 elevation, rapidly induces atrial electrical remodeling by down\u2010regulating cardiac connexins. Although transient, these changes may significantly increase the risk for atrial fibrillation and related complications during active inflammatory processes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.011006","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T09:02:05Z","timestamp":1566205325000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":186,"title":["Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin\u20106\u2013Mediated Changes in Connexin Expression"],"prefix":"10.1161","volume":"8","author":[{"given":"Pietro Enea","family":"Lazzerini","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Surgery and Neurosciences University of Siena 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