Figure 1.

VWF-deficient mouse shows impaired wound healing and reduced angiogenesis. Full-thickness back-skin wounds were made in WT and VWF-deficient mice. After 5 days, (A) wound closure and (B) granulation tissue area were evaluated by histomorphometry. (WT, n = 6; VWF-deficient, n = 7). (C) Wound histology (hematoxylin and eosin staining). Black arrows indicate tips of the epithelium tongue. The granulation tissue (pink-violet) is characterized by infiltration of granulocytes with nuclei stained in dark-violet or black. Muscle under the wounds is stained in red; fat tissue appears as transparent bubbles. Scale bar = 800 µm. Proliferation of (D) CD31⁺CD45^– ECs and (E) SMA⁺CD45^– SMCs assessed by Ki67⁺ marker was determined using flow cytometry. The amounts of (F) VEGF-A and (G) FGF-2 in the wounds were quantified by enzyme-linked immunosorbent assay (ELISA). (H-I) Representative high-magnification image by immunofluorescence and (J) quantification of VEGF-A in mouse skin wound healing sections from WT and VWF-deficient mice; sections are costained for VWF (green), SMA (red), and CD31 (yellow) to visualize blood vessels; nuclei are identified by 4′,6-diamidino-2-phenylindole (DAPI) (blue). Scale bar = 10 μm. (J) Quantification represents the ratio between the sum of pixel intensity for VEGF-A signal and DAPI volume (μm³) (n = 2 fields per mouse; n = 5 mice per genotype). Graphical data are mean ± standard error of the mean (SEM), Statistical comparisons were carried out using the Mann-Whitney U test. AU, arbitrary unit. *P < .05; **P < .01.