{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:07:13Z","timestamp":1789117633930,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Periodontitis is a chronic inflammatory disease initiated by dysbiotic subgingival biofilms and characterized by local tissue destruction, epithelial ulceration, immune-cell activation, and extracellular-matrix remodeling. Increasing evidence suggests that periodontal inflammation may extend beyond the oral cavity through recurrent bacteremia, dissemination of microbial products, systemic cytokine activation, endothelial dysfunction, oxidative stress, and thrombo-inflammatory signaling. These mechanisms are also implicated in atrial structural remodeling and atrial fibrillation (AF), but the molecular bridge between periodontal lesions, systemic inflammatory\u2013fibrotic activity, and the atrial substrate remains incompletely defined. This structured narrative review synthesizes mechanistic, translational, biomarker-based, observational, and interventional evidence linking periodontal inflammation with cardiovascular remodeling and AF. Literature was identified through searches of PubMed\/MEDLINE, Scopus, and Web of Science, complemented by reference-list screening. Particular attention was given to thrombospondin-1 (TSP-1), transforming growth factor-\u03b2 (TGF-\u03b2)-related signaling, galectin-3 (Gal-3), and SGLT2-related cardiometabolic pathways. Because of heterogeneity in study populations, periodontal definitions, biomarker measurements, interventions, and cardiovascular endpoints, findings were synthesized thematically rather than quantitatively. Periodontitis is associated with systemic inflammatory activation, endothelial dysfunction, oxidative stress, and cardiovascular phenotypes, including atherosclerotic disease, hypertension, heart failure, and AF. Epidemiological studies support an association between periodontitis and incident AF, while human tissue data link periodontal inflammatory burden with atrial fibrosis, non-paroxysmal AF, and left atrial appendage thrombosis in selected AF populations. The strength of evidence differs across the proposed pathways: Gal-3 has the most consistent clinical evidence in AF and cardiac fibrosis; TSP-1\/TGF-\u00df signaling is supported mainly by mechanistic periodontal-tissue and selected cardiovascular studies; and SGLT2-related pathways remain indirect systemic modifiers of the cardiometabolic and inflammatory milieu. Evidence regarding periodontal therapy and AF-related outcomes remains promising but limited and does not establish a direct antiarrhythmic effect. The available evidence supports a biologically plausible inflammatory\u2013fibrotic continuum linking periodontitis, systemic immune activation, endothelial dysfunction, atrial remodeling, and AF susceptibility. However, causality, temporal sequence, tissue-level concordance, and biomarker-based clinical utility remain insufficiently established. Future studies integrating standardized periodontal assessment, circulating biomarkers, tissue-level inflammatory\u2013fibrotic markers, cardiac imaging, and rhythm monitoring are needed to clarify whether local periodontal molecular signatures reflect systemic or cardiac remodeling relevant to AF vulnerability.<\/jats:p>","DOI":"10.3390\/ijms27188076","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:17:42Z","timestamp":1789114662000},"page":"8076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Periodontal Inflammation to Atrial Fibrillation: Molecular Links Through Thrombospondin-1, Galectin-3, and SGLT2-Related Pathways"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3362-0129","authenticated-orcid":false,"given":"Violeta Ariana","family":"Nicoras","sequence":"first","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Florin","family":"Lighezan","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, 1st Internal Medicine Department, 1st Medical Semiology Discipline, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7896-1253","authenticated-orcid":false,"given":"Horia Silviu","family":"Branea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I\u2014Medical Semiotics II, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Internal Medicine I\u2014Discipline of Internal Medicine IV, Department V, Center of Advanced Research in Cardiology and Hemostaseology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5258-670X","authenticated-orcid":false,"given":"Diana Alexandra","family":"Mitu","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Cardiovascular Pathology and Hemostaseology, 1st Internal Medicine Department, 1st Medical Semiology Discipline, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1059-7582","authenticated-orcid":false,"given":"Romina Georgiana","family":"Bita","sequence":"additional","affiliation":[{"name":"2nd Department, Radiology and Medical Imaging, General and Dento-Maxillary Imaging, Dental Medicine Faculty, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kong, P., Cui, Z.Y., Huang, X.F., Zhang, D.D., Guo, R.J., and Han, M. 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