Periodontal disease, specifically periodontitis, affects >40% of adults in the United States over the age of 30 years and increases the risk of ischemic stroke. The mechanisms underlying the increased risk of cerebrovascular events risk are poorly understood. Circulating endothelial cell-derived microvesicles (EMVs) are both a biomarker and mediator of vascular health and disease. The aims of this study was to determine: 1) whether circulating EMVs are elevated in adults with periodontitis; and 2) the effect of circulating EMVs isolated from adults with periodontitis on brain endothelial cell, oxidative stress, nitric oxide (NO) and endothelin (ET)-1 production in vitro. Twenty-four sedentary adults were studied: 12 without periodontitis (8 M/4F; age:50±3 yr; BMI: 28.8±1.0 kg/m 2 ) and 12 with periodontitis (7 M, 5 F; 56±5 yr; 26.7±1.7 kg/m 2 ). EMV identification (CD144+) and isolation from peripheral blood was performed by flow cytometry. Human cerebral microvascular endothelial cells (hCMECs) were cultured and treated with EMVs from each subject. Cells were harvested and intracellular reactive oxygen species (ROS) production was determined using CellROX Deep Red Reagent and expression of key antioxidant defense proteins (superoxide dismutase 1 (SOD-1) and catalase) and well as expression of endothelial NO synthase (eNOS), Big ET-1 and endothelin converting enzyme were determined by capillary electrophoresis immunoassay. NO and ET-1 production was determined by enzyme immunoassay. Circulating EMV concentrations were significantly higher in adults with vs without periodontitis (234±63 vs 153±28 EMV/μL; P< 0.001). ROS production was significantly higher (~30%) in hCMECs treated with EMVs from adults with periodontitis (118+29 vs 92+20%). Concordantly, expression of SOD-1 (11.9+1.9 vs 18.9+4.5 AU; P< 0.001) and catalase (10.0+3.2 vs 14.2+3.4 AU; P=0.005) were markedly lower in cells treated EMVs from adults with periodontitis, indicative of a cellular response to increased oxidative burden. Expression of phosphorylated (p)-eNOS (Ser1177) was lower (22.2±4.4 vs 27.1±5.5 AU; P=0.02) in cells treated with EMVs from adults with periodontal disease. As a result, NO production was markedly lower in cells treated with periodontitis-related EMVs (8.3±1.0 vs 9.6±1.6 μmol/L; P=0.02). Endothelial cell expression of Big ET-1 (46.9±15.1 vs 33.5±9.0 AU; P=0.01) and ET-1 production (36.4±6.5 vs 31.0±4.5 pg/mL; AU; P=0.03) were higher in cells treated with EMVs from adults with periodontal disease. In summary, circulating EMVs are elevated in adults with periodontitis; and negatively affect brain microvascular endothelial cell oxidative stress, antioxidant defense, eNOS activation, NO bioavailability and ET-1 production. Circulating EMVs may contribute to the increased risk of ischemic stroke with periodontitis by impairing brain microvascular endothelial cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Orozco-Fersiva et al. (Fri,) studied this question.