{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:13:35Z","timestamp":1790892815219,"version":"4.1.0"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap\u2010junctions containing connexin43 coupling cardiomyocytes and inflammation\u2010related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms.<\/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\">We analyzed: (1) the PR\u2010interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)\u20106 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C\u2010reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL\u20106. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL\u20106 changes. Moreover, direct IL\u20106 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL\u20106 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL\u20106\u2010induced down\u2010regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022095","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T09:07:36Z","timestamp":1635498456000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine\u2010Mediated Inhibition of Connexin43 Expression"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1214","authenticated-orcid":false,"given":"Pietro Enea","family":"Lazzerini","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena 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