1. EphrinB2/EphB4 signaling regulates the degree of vascular enlargement by VEGF dose
EphrinB2/EphB4 signaling regulates the degree of vascular enlargement by VEGF dose Mouse limb muscles were implanted with myoblast clones expressing low (V‐low) or high (V‐high) VEGF doses, while the ephrinB2/EphB4 signaling pathway was inhibited by co‐expression of the sEphB4 blocker (V‐low sEphB4) or stimulated by intraperitoneal treatment with ephrinB2‐Fc or control Fc protein. A–DImmunostaining of frozen sections (upper panels) stained for endothelium (CD31, red), pericytes (NG2, green), smooth muscle cells (α‐SMA, cyan), and nuclei (DAPI, blue) and quantification of vessel diameter distribution (lower panels) showed that 4 days after VEGF delivery, the size of initial circumferential enlargements was increased by ephrinB2/EphB4 inhibition and reduced by its stimulation (A, B). By 7 days, after completion of remodeling, EphB4 inhibition switched normal angiogenesis by V‐low to aberrant (C) and its stimulation converted aberrant structures by V‐high into normal capillary networks (D). Red arrows and numbers indicate the fraction of vessel diameters > 10 μm. *lumen of aberrant structures; mf, muscle fibers; scale bar, 25 μm.E–HQuantification of vessel diameters after 4 days (E, F) and 7 days (G, H). Values represent means of individual measurements in each sample ± SEM. n = 3–4 independent samples/group; *P < 0.05 and **P < 0.01 (one‐tailed t‐test, after data normalization by logarithmic‐transformation).
Elena Groppa et al. EMBO Rep. 2018;embr
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