Fig. 4: CCM lesions exhibit increased caveolae vesicles and Cav1-Tie2 signaling.

a–i Caveolae and Cav1-Tie2 signaling characterization in the early lesion model. Pdcd10^BECKO pups were fed with tamoxifen at P1 to P3 and tissues were harvested at P15. a–d Caveolae characterization in CCM lesions by EM. Cerebral sections from WT and Pdcd10^BECKO mice were subjected to EM. Representative images from 5 mice are shown. a Caveolae was indicated by asterisks while clathrin-coated pit by #. b Caveolae localization and forms. Luminal invagination, intracellular caveolae, and caveolae rosettes (clusters) are indicated. c Mean vesicular pit density at luminal and abluminal sides are quantified per 10 mm². d Mean vesicular pit density at intracellular, junctional, and rosettes are quantified per 10 mm². 20 EM section per mouse and n = 5. Data are means ± SEM. P values are indicated, unpaired two-sided Student’s t-test. e–g Cav1-Tie2 signaling was upregulated in mouse CCM lesions. Cerebral sections from WT and Pdcd10^BECKO mice were immunostained for Cav1 with CD31 (e), Tie2 (f), or p-Tie2 (g). Representative merged images of normal vessels (arrowheads) and CCM lesions (asterisks) are shown with individual color images of Pdcd10^BECKO at the bottom. n = 6. h, i Tie2 was not localized in EC nucleus. Brain sections from WT and Pdcd10^BECKO mice were co-stained with Tie2 and Cldn5 (h) or p-Tie2 and Cldn5 (i). Images were captured under SP8 STED microscopy. Representative images for WT normal vessels (arrowheads) and CCM lesions (asterisks) in Pdcd10^BECKO mice are shown with individual color images of Pdcd10^BECKO at the bottom. n = 6. j, k Cav1-Tie2 signaling was upregulated in human CCM lesions. Human CCM specimens were co-immunostained for CD31 and Cav1 with Tie2 (j) or p-Tie2 (k). Representative images of human CCM3 samples captured under SP8 STED microscopy are shown with high-power merged 4-color images on the right. n = 6. Arrowheads indicate normal vessels whereas asterisks indicate for lesions. Scale bar: 500 nm (a); 150 nm (b); 25 μm (e; left and middle panels in (j) and (k)); 8 μm (h, i; right panels in (j) and (k)). Source data are provided as a Source data file.