Abstract
Transforming growth factor β1 (TGF-β1) has been implicated in both the stimulation of angiogenesis in vivo and in the inhibition of endothelial cell proliferation in in vitro systems. In this study we present evidence showing that under certain experimental conditions TGF-β1 may inhibit neovascularization in vivo. TGF-β1 was incorporated into ethylene vinyl acetate copolymer (Elvax 40) matrixes which provide a valuable vehicle for the controlled and sustained delivery of bioactive peptides. The biological effectiveness of TGF-β1 sequestered in polymer matrices was assessed by measuring the inhibition of [3H]-thymidine incorporation into the DNA of cultured mink lung epithelial cells. Neovascularization was induced in both corneas of albino rabbits by one deep-seated limbal silk suture. Elvax 40 matrixes loaded with TGF-β1 (release rate, 1.66 ng/24 h) were implanted in rabbit corneal stroma. 'Empty' polymers in the contralateral eye served as controls. Aliquots of aqueous fluid were withdrawn, and the presence activity of phagocytic cells was assessed by the production of superoxide anion (O2-) which was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C. Polymer-enclosed TGF-β1 implanted in rabbit corneas significantly suppressed angiogenesis (2.65 ± 0.4 mm compared to 3.05 ± 0.3 mm in contralateral controls p < 0.05). Superoxide production in 100 μl aliquots of aqueous fluid was 0.95 ± 0.18 and 0.6 ± 0.18 nmol O2-/10 min in control eyes and in the eyes bearing sequestered TGF-β1, respectively (p < 0.02). These results indicate that under the experimental conditions selected in this study, TGF-β1 significantly suppressed in vivo angiogenesis.
Original language | English |
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Pages (from-to) | 59-64 |
Number of pages | 6 |
Journal | In Vivo |
Volume | 10 |
Issue number | 1 |
State | Published - 1 Jan 1996 |
Keywords
- Angiogenesis
- Chemotaxis
- Neovascularization
- Polymer
- Transforming growth factor-β
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- Pharmacology
- Cancer Research