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This study aimed to investigate the role of\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      OMVs in vascular endothelial glycocalyx injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this clinical study, serum levels of syndecan-1 (SDC1) and heparan sulfate (HS), biomarkers of endothelial glycocalyx injury, were measured and compared between patients with stage III-IV periodontitis and those with stage I-II or no periodontitis. Then, glycocalyx injury was detected using transmission electron microscopy, immunofluorescence and western blotting after vascular endothelial cells were stimulated and C57BL\/6J mice were administered with\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      OMVs via tail vein injection. Transcriptomic high-throughput sequencing analysis and in vitro and in vivo rescue experiments were conducted to determine the key mechanism in glycocalyx injury. Experiments were conducted using OMVs,\n                      <jats:sup>PPAD\u2212OE<\/jats:sup>\n                      OMVs, and\n                      <jats:sup>\u0394PPAD<\/jats:sup>\n                      OMVs to identify the special virulence factors in OMVs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This study revealed that serum levels of SDC1 and HS were significantly higher in patients with stage III-IV periodontitis (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). A marked reduction in both the fluorescence intensity of the glycocalyx and the expression levels of its key components was observed in the OMVs group compared with control group (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). We identified the key differentially expressed gene\n                      <jats:italic>B3GAT1<\/jats:italic>\n                      using high-throughput sequencing. Subsequent rescue experiments both in vitro and in vivo demonstrated that overexpression of B3GAT1 effectively restored glycocalyx integrity following injury (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Notably,\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      peptidylarginine deiminase (PPAD) was found to promote endovascular glycocalyx injury by citrullinating histone H3, thereby decreasing the expression of B3GAT1 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our experiments demonstrated that biomarkers of endothelial glycocalyx injury were significantly higher in patients with stage III-IV periodontitis and PPAD could enter the cell nucleus, playing a vital role in vascular endothelial glycocalyx injury through the CitH3\/B3GAT1 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-025-04015-4","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T04:54:13Z","timestamp":1767934453000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Porphyromonas gingivalis-derived outer membrane vesicles promote vascular endothelial glycocalyx injury via the PPAD\/CitH3\/B3GAT1 pathway"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-2526","authenticated-orcid":false,"given":"Shoucheng","family":"Yin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6276-0468","authenticated-orcid":false,"given":"Qihui","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaorong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzhou","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziming","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-8992","authenticated-orcid":false,"given":"Yaping","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-8007","authenticated-orcid":false,"given":"Li","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"issue":"1","key":"4015_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/prd.12323","volume":"82","author":"PI Eke","year":"2020","unstructured":"Eke PI, Borgnakke WS, Genco RJ. 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