oxLDL enhances platelet procoagulant activity in vivo. (A) Wild-type C57BL/6J mice (median age, 6 weeks) were intravenously injected with vehicle (phosphate-buffered saline) alone or oxLDL 10 minutes before blood collection into citrate (n = 5 per condition). Whole blood samples were analyzed for platelet-monocyte aggregate formation as previously described.^35,49 (B) Whole blood samples from vehicle- and oxLDL-injected animals were subsequently stimulated with GPVI agonist (0.1 μg/mL CRP-XL) before flow cytometry analysis of CD62P as a marker of platelet α-granule secretion. (C) Sets of mice (n = 5 each) were administered by vehicle (dimethyl sulfoxide), ticagrelor (100 mg/kg), aspirin (30 mg/kg), or ibrutinib (10 mg/kg) by intraperitoneal injection before oxLDL injection, blood collection, and flow cytometry analysis of FITC-lactadherin to follow platelet PS exposure. (D) Aliquots of citrate-anticoagulated whole blood from obese rhesus macaques (detailed in Figure 1, in previous section) were pretreated with vehicle (dimethyl sulfoxide), ticagrelor, aspirin, or ibrutinib before stimulation with GPVI agonist (0.1 μg/mL CRP-XL), lactadherin-FITC staining, and flow cytometry assessment of platelet PS exposure. Statistical analysis was performed using a one-way ANOVA test and the corresponding P values of significance are as indicated: ∗P < .01.