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Inhibition by acharan sulphate of angiogenesis in experimental inflammation models
Author(s) -
Ghosh Ajoy Kumar,
Hirasawa Noriyasu,
Lee Yeon Sil,
Kim Yeong Sik,
Shin Kuk Hyun,
Ryu Nama,
Ohuchi Kazuo
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704886
Subject(s) - granulation tissue , angiogenesis , inflammation , granulation , pouch , chemistry , vascular endothelial growth factor , endocrinology , medicine , biology , wound healing , immunology , anatomy , vegf receptors , materials science , composite material
The effects of acharan sulphate, a glycosaminoglycan isolated from the giant African snail Achatina fulica , on angiogenesis in the granulation tissue were analysed using an air pouch‐type carrageenin‐induced inflammation model in rats and a cotton thread‐induced inflammation model in mice. In the carrageenin‐induced inflammation model in rats, intra‐pouch injections of acharan sulphate (5 and 50 μg) inhibited the pouch fluid accumulation and the granulation tissue formation as well as the angiogenesis in the granulation tissue at day 6 in a dose‐dependent manner. The inhibitory effects of acharan sulphate at 50 μg on the pouch fluid accumulation and the leucocyte infiltration into the pouch fluid was not so effective as that of the cyclo‐oxygenase inhibitor indomethacin at 100 μg, but the inhibitory effects of acharan sulphate at 50 μg on the granulation tissue formation and angiogenesis in the granulation tissue were almost the same as those of indomethacin at 100 μg. Acharan sulphate did not affect levels of vascular endothelial growth factor (VEGF) in the granulation tissue and in the pouch fluid at day 6, but indomethacin significantly lowered them. In the cotton thread‐induced inflammation model in mice, injections of acharan sulphate (10 μg) at the site of the cotton thread implantation inhibited the granulation tissue formation and angiogenesis as indomethacin (20 μg) did. Acharan sulphate (10 μg) did not affect levels of VEGF in the cotton thread‐induced granulation tissue at day 5, but indomethacin (20 μg) significantly lowered them. In culture of human vascular endothelial cells, acharan sulphate at 10 and 100 μg ml −1 inhibited VEGF‐induced capillary tube formation. These findings suggest that the inhibitory effect of acharan sulphate on angiogenesis in carrageenin‐ and cotton thread‐induced granulation tissues is not due to the inhibition of VEGF protein induction, but is due to the inhibition of VEGF‐induced vascular tube formation.British Journal of Pharmacology (2002) 137 , 441–448. doi: 10.1038/sj.bjp.0704886