Increased EPCR in CCMs. (A) Immunohistochemistry of EPCR (brown precipitate) of human CCMs and brain tissue from a healthy subject as control. Asterisks denote vascular lumen of CCM lesions. Scale bar, 100 μm (n = 3). (B) Analysis of PROCR (EPCR) mRNA levels by RT-qPCR in human CCM lesions or control brain tissue in (A) (SEM, n = 4 CCM tissue, n = 1 lesion-free brain tissue from CCM patient, n = 2 healthy subject brain tissue, and n = 2 postmortem specimens as control). (C) RT-qPCR analysis of Procr (Epcr) mRNA in Krit1^ECKO or Pdcd10^ECKO BMECs compared with Krit1^fl/fl or Pdcd10^fl/fl BMECs (control), respectively (SEM, n = 3). (D) Quantification of EPCR protein in 9-day Krit1^ECKO (KO) BMECs compared with Krit1^fl/fl (Flox) BMECs (SEM, n = 3). (E) Quantification of EPCR protein in 20-day Pdcd10^ECKO (KO) BMECs compared with Pdcd10^fl/fl (Flox) BMECs (SEM, n = 3). (F) Analysis of Epcr mRNA levels by RT-qPCR in cerebellar, heart, intestine, and lung tissue in Pdcd10^ECKO mice and control Pdcd10^fl/fl littermates (SEM, n = 4 or 7 mice in each group). (G) Analysis of EPCR protein levels in human umbilical vein endothelial cells transduced with lentivirus encoding KLF2 or KLF4, as assessed by western blot analysis; lentivirus encoding GFP was used as control (SEM, n = 3). (H) Analysis of EPCR mRNA levels by RT-qPCR in human umbilical vein endothelial cells transduced with lentivirus encoding KLF2 or KLF4 compared with lentivirus encoding GFP as control (SEM, n = 3 or 4). *P < .05, Student t test and 1-way ANOVA, followed by the Tukey post hoc test.