Inhibition of shear-dependent platelet MV release and PS exposure in mouse and human platelets by mP6, a peptide inhibitor of Gα13-integrin interaction and outside-in signaling. (A) Effects of mP6 or a negative control peptide (AAA mutant, Myr-FAAARA) on MV release from mouse platelets stimulated by 0.05 U/mL of thrombin with shear of 3000 s−1 as analyzed by flow cytometry. (B) Effects of mP6 or a control peptide on PS exposure on mouse platelets stimulated by 0.05 U/mL of thrombin with shear of 3000 s−1 as indicated by annexin V binding. (C) Effects of mP6 or a control peptide on MV release from human platelets stimulated with 0.05 U/mL of thrombin with or without shear. (D) Effects of mP6 (40 µM) or a control peptide on PS exposure on human platelets stimulated with 0.05 U/mL of thrombin with or without shear. (E) MV release from thrombin- and shear-stimulated mouse platelets treated with dimethyl sulfoxide (DMSO; vehicle control), Src inhibitor PP2, integrin antagonist integrilin, or Rac1 inhibitor NSC23766. (F) PS exposure on thrombin- and shear-stimulated platelets treated with DMSO, PP2 (10 µM), integrilin (20 µg/mL), or NSC23766 (100 µM). (G) MV release from CRP- and shear-stimulated platelets treated with DMSO, PP2, integrilin, or NSC23766. (H) PS exposure on CRP- and shear-stimulated platelets treated with DMSO, PP2, integrilin, or NSC23766. Data are presented as mean ± standard error of the mean (n = 3-4). **P < .01, ***P < .001, and ****P < .0001.
