Background:　The　outer　membrane　vesicles　(OMVs)　derived　from　Porphyromonas　gingivalis　(P.　gingivalis)　have　long　been　acknowledged　for　their　crucial　role　in　the　initiation　of　periodontitis.　However,　the　implications　of　P.　gingivalis　OMVs　in　the　context　of　cardiovascular　disease　(CVD)　remain　incompletely　understood.　This　study　aimed　to　clarify　both　the　impact　and　the　underlying　mechanisms　through　which　P.　gingivalis　OMVs　contribute　to　the　propagation　of　distal　cardiovascular　inflammation　and　trauma.　Methods:　In　this　study,　various　concentrations　(0,　1.25,　2.5,　and　4.5 µg/µL)　of　P.　gingivalis　OMVs　were　microinjected　into　the　common　cardinal　vein　of　zebrafish　larvae　at　48 h　post-fertilization　(hpf)　to　assess　changes　in　cardiovascular　injury　and　inflammatory　response.　Zebrafish　larvae　from　both　the　PBS　and　the　2.5 µg/µL　injection　cohorts　were　harvested　at　30 h　post-injection　(hpi)　for　transcriptional　analysis.　Real-time　quantitative　PCR　(RT-qPCR)　was　employed　to　evaluate　relative　gene　expression.　Results:　These　findings　demonstrated　that　P.　gingivalis　OMVs　induced　pericardial　enlargement　in　zebrafish　larvae,　caused　vascular　damage,　increased　neutrophil　counts,　and　activated　inflammatory　pathways.　Transcriptomic　analysis　further　revealed　the　involvement　of　the　immune　response　and　the　extracellular　matrix　(ECM)-receptor　interaction　signaling　pathway　in　this　process.　Conclusion:　This　study　illuminated　potential　mechanisms　through　which　P.　gingivalis　OMVs　contribute　to　CVD.　It　accentuated　their　involvement　in　distal　cardiovascular　inflammation　and　emphasizes　the　need　for　further　research　to　comprehensively　grasp　the　connection　between　periodontitis　and　CVD.　©　2024,　The　Author(s).