BTD carbon nucleophile decreases arterial thrombosis in dyslipidemia. BTD inhibits the prothrombotic platelet phenotype in “Western” high-fat diet-fed mice to chow-fed control levels using the FeCl₃-induced carotid artery thrombosis model. (A) Intravital microscopy video images of the carotid artery from mice fed chow or a high-fat diet treated with vehicle control or 25 mg/kg BTD. (B-C) Histograms of time to occlusion (B), and Kaplan-Meier curves of the fraction of vessels not occluded (C) are shown (P = .01 between Chow Diet + DMSO vs High Fat Diet + DMSO; P = .46 between Chow Diet + DMSO vs High Fat Diet + 25 mg/kg BTD). BTD rescued the enhanced platelet and fibrin accumulation induced by oxLDL in the laser ablation cremasteric artery thrombosis model (C). (D) Intravital microscopy images of the cremasteric artery from intravenously injected PBS or 2.5 mg/kg oxLDL-injected mice treated with vehicle or 25 mg/kg BTD. Platelets are red and fibrin is green. (E,G) Median integrated fluorescence intensity over time of platelets (E) and fibrin (G) are shown. (F,H) Quantification of the normalized platelet (F) and fibrin (H) accumulation as area under the curve (AUC) by the length of the injury are presented. In both thrombosis models, DMSO (as the vehicle treatment) and BTD were prepared in 20% v/v cremophore in PBS and were injected intraperitoneally 3 hours before injury. P values were determined by unpaired Student t test (B), log-rank (Mantel-Cox) Kaplan-Meier tests (C), and 1-way analysis of variance with Kruskal-Wallis pairwise comparisons (F,H). For the FeCl₃ thrombosis model, N = 6 mice for vehicle control treatment in conditions of a chow diet. N = 3 mice for vehicle control treatment, 3 mice for 25 mg/kg BTD treatment, 5 mice for 50 mg/kg BTD treatment, and 4 mice for 100 mg/kg BTD treatment in conditions of a high-fat diet. For the laser ablation thrombosis model, N = 3 mice for DMSO and 3 mice for BTD treatment and ≥22 injuries per PBS or oxLDL cohort of thrombosis. Data are expressed as mean ± SD.