Figure 6.
Complementary roles of PI3Kβ and PI3Kγ in stabilization of murine thrombi. (A) Formation of thrombi during flow over VWF/collagen at 1000 s–1 for 4 minutes, recorded by high-speed fluorescence imaging. Blood from wild-type and PI3Kγ–/– mice was labeled with nonblocking AF5-568–anti-GPIb mAb Xia.B2. Left panel shows representative x-y images; partitions represent x-z and y-z cross-sections. Right panel shows height of thrombi after 4 minutes. (B-C) Murine blood containing vehicle or TGX221 (1 μM) was flowed over VWF/collagen. (B) Representative phase-contrast images (120 × 120 μm) after secondary perfusion. (C) Disaggregation events from murine thrombi during 4 minutes of flow. (D) Disaggregation events from murine thrombi in the presence of AR-C69931MX (30 μM) with/without TGX221 (1 μM) or MRS2179 (100 μM). Indicated are numbers of embolizing events (single or clustered) platelets per aggregate. Data are means ± SEM (n = 3-5 experiments; *P < .05 vs vehicle).