Homocysteine inhibits angiogenesis in vitro and in vivo

Homocysteine has been reported to inhibit endothelial cell proliferation, w hich is closely related to angiogenesis. However, the relationship between homocysteine and angiogenesis is unknown. To clarify whether homocysteine w ould inhibit angiogenesis in vitro and in vivo, we examined the effect of h omocysteine on tube formation by bovine aortic endothelial cells (BAECs) an d by human microvessel endothelial cell-1 (HMEC-1) in vitro, and on angioge nesis in vivo using the chorioallantoic membrane (CAM) assay, as well as on BAEC proliferation and migration. Homocysteine, but not cysteine, inhibite d BAEC proliferation, migration, and tube formation in a dose dependent man ner at concentrations from 0 to 10 mM. Homocysteine also inhibited tube for mation by HMEC-1s. In these assay, 50% inhibition was induced by about 1 mM homocysteine. In the in vivo CAM assay, 0, 10, 100, 500, and 1000 mug homo cysteine induced an avascular zone by 0, 0, 16.7, 53.3 and 76.5%, respectiv ely, also showing a dose-dependent effect. It was suggested that homocystei ne inhibited angiogenesis by preventing proliferation and migration of endo thelial cells, (C) 2001 Academic Press.