Mice lacking endothelial apoER2 or expressing mutant forms of apoER2 incapable of interaction with Dab2 or p66 SHC1 are protected from aPL-induced thrombosis. (A) Control ApoER2^fl/fl or ApoER2∆EC male mice (4-6 weeks old) were injected with NHIgG or aPL (100 µg, IP), and, 24 hours later, aortas were isolated and PP2A activity was quantified; N = 5. (B-D) Mice were treated as described in panel A, and thrombus formation following ferric chloride initiation was evaluated in the mesenteric microcirculation by intravital microscopy. Representative still images taken 9 minutes after ferric chloride application are shown in panel B. The size of the largest thrombi formed within 9 minutes of initiation (C) and time to total occlusion were evaluated (D). (C-D) N = 5-7. (E-H) The impact of aPL on thrombus formation was evaluated in control WT mice (WT) and control mice with full-length apoER2 (FL), and in mice expressing mutant forms of apoER2 harboring an EIGNPVY substitution for NFDNPVA (EIG) or lacking the proline-rich C terminus of the receptor (ApoER2∆19) (N = 7-11). PP2A activity was measured in isolated aortas (E); representative images of thrombus formation 9 minutes after ferric chloride application are shown (F); and the size of the largest thrombi formed within 9 minutes (G) and time to total occlusion were evaluated (H). (B, F) The images were captured by a Nikon Eclipse Ti microscope and its camera system (Quantem 512SC, Plan Fluor, 10×, 0.3 aperture) at room temperature with fluorescein isothiocyanate as fluorochrome. NIS Elements software was used to capture and process the images. Scale bars, 50 µm. Values are mean ± SEM, ****P < .0001, ***P < .001, **P < .01, *P < .05.