Fig. 9. Downregulation of NOTCH4 in arteries associated with CCM from patients with loss-of-function mutations in CCM1. (A,B) Immunohistochemistry using antibodies against NOTCH4 on human tissues. (A) A section of normal brain taken from an autopsy specimen showing NOTCH4 signal from endothelium and vascular smooth muscle cells of two arteries (red arrowheads), without significant expression from an adjacent vein (blue arrow). (B) A section from a surgically excised specimen from a patient with a previously characterized mutation of CCM1 (Sahoo et al., 1999). An artery (red arrowhead) from brain tissue adjacent to a cavernous malformation shows little NOTCH4 protein in the endothelium or vascular smooth muscle cells. There is no NOTCH4 staining in an adjacent venule (blue arrow). Similar findings were present from two other members of the same family. Scale bars: 100 µm.