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A. S. Schering, S. Nakao, S. Zandi, A. Hafezi-Moghadam; Distinct Mechanisms Underlying Fgf-2 and Vegf-a Induced Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4974.
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Lymphangiogenesis is commonly accompanied by angiogenesis. In a recent work, Chang et al. showed that low dose FGF-2 induces primarily growth of lymphatic vessels, indicating that angiogenesis is not required for lymphangiogenesis. However, whether VEGF-A can induce selective lymphangiogenesis is unknown.
Hydron pellets (0.3µl) containing 25, 100, 200 or 400ng VEGF-A (497-MV; R&D Systems) or 100ng FGF-2 (3139-FB; R&D Systems) were prepared and implanted into corneas of C57BL/6J mice. For quantification, corneal flat mounts were generated on day 6 post implantation and angiogenic and lymphangiogenic vessels were visualized by CD31 and LYVE-1-staining, respectively.
VEGF-A implantation at 200ng/eye caused increased number of lymphatic vessels only in the front, but not in the side or in the back. Lymphatic vessels were located above limbal vessels in the side and back of VEGF-A-implanted corneas, as well as in untreated controls. The ratio of lymphatic vessel length to vascular length was significantly higher in FGF-2-implanted corneas compared with VEGF-A-implanted corneas in the side and in the back (side P=0.006, back P=0.0002, n=12-21). Implantation of 100 or 400ng VEGF-A caused substantial growth of new vessels (P=0.0002 and P=0.005, respectively, n=5-8), while 25ng VEGF-A implantation did not elicit a significant response (P=0.4, n=6-8). 100ng VEGF-A induced significant angiogenesis but not lymphangiogenesis (P=0.49, n=6). 400ng VEGF-A induced in addition to angiogenesis also significant lymphangiogenesis (P=0.007, n=5-6). However, even with 400ng VEGF-A the ratio of lymphatic vessel length to angiogenic vessel length did not differ significantly (P=0.8, n=15).
VEGF-A preferentially causes angiogenesis compared with secondary lymphangiogenesis, regardless of the implanted dose. Our results provide evidence for distinct mechanisms underlying FGF-2 and VEGF-A induced lymphangiogenesis.
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