Fig. 3. Effect of protease inhibitors on HUVEC and HDMEC tubulogenesis within fibrin gels. HUVECs (A,B,D,E) and HDMEC (C) were grown within fibrin gels in standard serum-containing EC medium and stimulated with VEGF (25 ng/ml) and FGF-2 (25 ng/ml). Protease inhibitors were added both to the gel and to the culture medium at the beginning of the experiment where indicated. aprot, aprotinin; pep, pepstatin. The cells were incubated at 37°C and 5% (v/v) CO₂ for 3 days, and the total tube length was calculated as described in the legend of Fig. 2. The average and s.d. of each experiment is shown. ^* indicates statistically significant differences (P<0.05) compared with the buffer control (^** P<0.0001). A significant difference (P<0.05) was also observed between full-length TIMP-2 and wild-type N-TIMP-2 in E.