Analysis of the response in the cremaster muscle to Ad-VEGF-DΔNΔC.

(A-C) Tissue sections of cremaster muscle 5 days after injection (hematoxylin and eosin staining; ×20 objective). (A) PBS induced moderate interstitial edema surrounding skeletal muscle. No vascular proliferation was seen. (B) Ad-GFP induced chronic inflammation consisting of lymphocytes and tissue monocytes with mild interstitial edema. No significant vascular proliferation. (C) Ad-VEGF-DΔNΔC induced interstitial edema and a central focus of vessels with the appearance of venous channels. Blood vessels are indicated by arrowheads. (D-F) Sections taken 3 weeks after injections were stained for laminin. Ad-VEGF-DΔNΔC induced a distinct increase in the number of laminin-positive blood capillaries; ×40 objective. (F) Higher magnification (×100 objective) is shown in the inset. Arrows indicate blood vessels. (G-L) Pairs of serial tissue sections from cremaster muscle 21 days after Ad-VEGF-DΔNΔC injection were stained for VWF (G) and laminin (H) and for VEGFR-2 (K, L) and laminin (I, J). A wide range of vascular, blood-filled, irregular venous channels could be identified between muscle fibers. Some were thin-walled with a single EC layer between the lumen and adjacent tissue. Blood vessels (bv) are shown and in some cases are denoted by arrowheads. Panels G-L, ×50 objective. (M, N) VEGFR-2 expression 21 days after treatment with Ad-VEGF-DΔNΔC. (O) Negative control. Panels M-O, ×100 objective.