Phosphatidylserine Exposure: The Hidden Thrombotic Threat Of Periodontitis With T2d

To explore how neutrophil extracellular traps (NETs) and phosphatidylserine exposure contribute to hypercoagulability in periodontitis with type 2 diabetes . Sixty-four participants were divided into groups with periodontitis (CP), T2D, periodontitis with type 2 diabetes (DP), and a healthy control group (CTR). Participants were recruited from a university-affiliated hospital in Harbin between December 2023 and December 2024. The study was approved by the relevant ethics committee. Coagulation profiles were assessed using coagulation time and fibrin generation tests. Confocal microscopy and flow cytometry were employed to measure PS-exposed cells and NETs in blood samples. The impact of NETs on endothelial cells was evaluated through western blot, confocal microscopy, and angiogenesis assays. DP patients showed significantly shorter coagulation times, higher fibrinogen levels, and increased numbers of blood cells (e.g. platelets and neutrophils) with phosphatidylserine (PS) exposure, along with increased NETs release. PS+ platelets were found to stimulate NETs release more than microparticle-poor plasma. NETs damage vascular endothelial cells, leading to increased VCAM-1, decreased VE-cadherin, actin reorganization, reduced tube formation, and higher procoagulant activity in endothelial cells. These effects were reduced by DNase I inhibition of NETs. In DP patients, PS+ platelets trigger neutrophils to release excess NETs, contributing to a pro-thrombotic state by damaging endothelial cells.