{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:06:18Z","timestamp":1779379578245,"version":"3.53.1"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      This study investigates whether periodontitis exacerbates atherosclerosis (AS) by inducing an inflammatory response and macrophage pyroptosis through\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      lipopolysaccharide (\n                      <jats:italic>P.g.\u2010<\/jats:italic>\n                      LPS)\u2010mediated activation of the NF\u2010\u03baB\/NLRP3\/caspase\u20101 pathway, aiming to identify potential therapeutic targets linking periodontal inflammation to atherosclerotic cardiovascular disease (ASCVD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Apolipoprotein E\u2010deficient (ApoE\u2212\/\u2212) mice fed a high\u2010fat diet (HFD) were used as AS models, with periodontitis induced by molar ligation and\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      application. Plaque levels, serum lipids, serum pro\u2010inflammatory markers, and aortic protein expression were assessed. In vitro, THP\u20101 macrophages were treated with oxidized low\u2010density lipoprotein (ox\u2010LDL) and\/or\u00a0\n                      <jats:italic>P.g<\/jats:italic>\n                      .\u2010LPS, with or without the NLRP3 inhibitor MCC950. Pyroptosis (LDH release) and pathway activation were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vivo, the ApoE(\u2212\/\u2212) + HFD + periodontitis group exhibited more severe intimal hyperplasia (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and upregulated aortic expression of TLR4, NLRP3(the core sensor of the inflammasome), F4\/80 (a specific murine macrophage marker), and Gasdermin D (GSDMD) (the executor of pyroptosis) versus ApoE(\u2212\/\u2212) + HFD controls (all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). In vitro, ox\u2010LDL and\n                      <jats:italic>P.g.\u2010<\/jats:italic>\n                      LPS co\u2010treatment in THP\u20101 cells synergistically increased LDH and IL\u20101\u03b2 release (all adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and maximally induced mRNA\/protein levels of the NF\u2010\u03baB\/NLRP3\/caspase\u20101\/GSDMD axis. Critically, this synergistic effect was abrogated by MCC950, confirming the centrality of NLRP3 inflammasome activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal a key mechanistic link between periodontitis and atherosclerosis progression, demonstrating that NF\u2010\u03baB\/NLRP3\/caspase\u20101\u2010mediated macrophage pyroptosis serves as a critical pathogenic bridge. These results identify this inflammatory cell\u2010death pathway as a potential focal point for understanding and intervening in the exacerbation of ASCVD by periodontal infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that periodontitis exacerbates atherosclerosis (AS) through in vivo and in vitro models. In ApoE(\u2013\/\u2013) mice fed a high\u2010fat diet, periodontitis aggravated aortic plaque formation, elevated pro\u2010inflammatory cytokines, dyslipidemia, and enhanced macrophage pyroptosis compared to AS controls. Mechanistically,\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      lipopolysaccharide (\n                      <jats:italic>P.g.\u2010<\/jats:italic>\n                      LPS) synergized with ox\u2010LDL to activate the NF\u2010\u03baB\/NLRP3\/caspase\u20101 pathway in macrophages, driving pyroptosis and amplifying inflammatory responses. This synergistic effect was blocked by the NLRP3 inhibitor MCC950. These findings identify the NF\u2010\u03baB\/NLRP3\/caspase\u20101 axis as a pivotal link between periodontal inflammation and AS progression, suggesting that targeting this pathway might represent a potential therapeutic avenue for mitigating atherosclerotic cardiovascular disease (ASCVD) risk associated with periodontal disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70146","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:20:31Z","timestamp":1779376831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Periodontitis aggravates atherosclerosis by inducing inflammatory response and macrophage pyroptosis through the NF\u2010\u03baB\/NLRP3\/caspase\u20101 pathway"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7409-3137","authenticated-orcid":false,"given":"Bin","family":"Su","sequence":"first","affiliation":[{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"},{"name":"Department of Cardiology The Third Central Hospital of Tianjin Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Stomatological Hospital School of Medicine Nankai University Tianjin China"},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Clinical Laboratory The Third Central Hospital of Tianjin Tianjin 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