Figure 7. TF+ tumor microvesicles enhance thrombosis in mice in a platelet-dependent manner.
(A–C) Par4 KO mice (−/−) or WT (+/+) littermate controls underwent the inferior vena cava (IVC) stenosis model followed by injection of BxPc-3 MVs at 5 minutes, 30 minutes, and 1 hour (9 μg total). (A) Thrombus development was quantified by high-frequency ultrasonography. Data were analyzed by one-way ANOVA and are statistically significant for Par4+/+ + MVs versus Par4−/− + MVs. P<0.001, Par4+/+ n=6, Par4−/− n=5. (B) Percent incidence of thrombosis is shown from the thrombosis experiment in panel A. No difference was found by log-rank sums test. (C) Mouse survival following MV injection in panel A is reported with death defined as permanent cessation of breathing within 5 minutes of MV injection. Survival data were analyzed by log-rank (Mantel-Cox) test. (D-F) Clopidogrel or vehicle treated wild-type mice were subjected to IVC stenosis followed by BxPc-3 MV injection as above and (D) thrombus formation was quantified by high-frequency ultrasonography. Data were analyzed by one-way ANOVA and are statistically significant for MVs + clopidogrel versus MVs + vehicle control. P<0.001, BxPc-3 MVs + vehicle n=5, BxPc-3 MVs + clopidogrel n=6. (E) Percent incidence of thrombosis is shown from the thrombosis experiments in panel D. No difference was found by log-rank sums test. (F) Mouse survival following MV injection in panel D is reported with death defined as permanent cessation of breathing within 5 minutes of MV injection. Survival data were analyzed by log-rank (Mantel-Cox) test.