Injection of MVs with a high level of PGC improves survival and reduces clot formation in a murine model of sepsis. (A) Cecal ligation was performed on CD-1 mice (n = 36 animals). Each group of animals received a daily IV tail injection (D1 to D4) of uPA-Gran-MVs or Gran-MVs or SPN uPA-Gran-MVs from D1 (24 hours after surgery). Once sepsis was established, mice were observed daily to assess spontaneous mortality and monitored to measure their heart rate, oxygen saturation, breathing rate, and body temperature. The animals were sacrificed at D5. (B-C) Temperature amplitude at D1 (°C) and the clinical score of 3 groups of animals injected with uPA-Gran-MVs (red circle), Gran-MVs (blue square), or SPN uPA-Gran-MVs (green triangle) (n = 12 animals per group). Data are mean ± SEM. (D) Coagulolytic balance (MV-PGC and MV-TF) of uPA-Gran-MVs (10⁷) (red), Gran-MVs (10⁷) (blue), supernatant (SPN-uPA-Gran-MVs) (green), and Mono-MVs (10⁷) (purple); n = 3. (E) Survival curve of animals (n = 12 in each group). The results are presented as the percent survival. (Fa,c) Count of microthrombi in kidney and lung tissues after hematoxylin-eosin and phosphotungstic acid-hematoxylin staining (PTAH; uPA-Gran-MVs n = 10, red circle; Gran-MVs n = 6, blue square; SPN uPA-Gran-MVs n = 7, green triangle). Data are mean ± SEM. (Fb,d) Histopathology of lung and kidney tissue samples from different groups of mice. Injected with uPA-Gran-MVs (n = 11); injected with Gran-MVs (n = 6); control group injected with SPN uPA-Gran-MVs (n = 6). Microthrombi are indicated by black arrows; black bar = 100 µm. (G) Survival curve of animals injected in uPA-Gran-MVs (10⁷) (red), soluble uPA (orange), or SPN-uPA-Gran-MVs (green) (n = 12 in each group). The results are presented as the percent survival. *P < .05; **P < .01; ***P < .001; NS: not significant.