The proteolytic fragment of collagen XVIII, endostatin, acts as an inhibitor of angiogenesis. To date, only limited knowledge exists on the effects of endostatin on endothelial cells during embryonic development. Therefore, we analysed the role of endostatin on embryonic vasculo- and angiogenesis. Endostatin is accumulated in embryonic tissue of mouse embryos. Similarly, in vessels of embryoid bodies (EBs), endostatin and its binding sites are distributed in vessels and sprouting areas. In EBs, endostatin increases endothelial cells (control, 279.3 +/- 76.5; 50 ng/ml, 566.3 +/- 90.1; 200 ng/ml, 594.5 +/- 166.3 tube-like structures per EB) and endothelial tubes by proliferation (control, 21.4 +/- 7.5; 50 ng/ml, 160.2 +/- 9.9; 200 ng/ml, 184.2 +/- 16.5 Ki67-positive nuclei per 50 tube-like structures); it also enhances migration (control, 380.5 +/- 159.8 cells; 50 ng/ml, 718.3 +/- 251 cells; 200 ng/ml, 706 +/- 89.4 cells) and apoptosis (control, 16.8 +/- 6.7; 50 ng/ml, 94.4 +/- 23.6; 200 ng/ml, 106 +/- 42 PARP-positive nuclei per 50 tube-like structures). Furthermore, endostatin modulates the morphology of the endothelial tubes by inducing contraction. Endostatin modulates the embryonic vascular development by enhancing proliferation, migration, and apoptosis as well as by regulating morphogenesis.
Copyright 2004 Wiley-Liss, Inc.