Paracrine or virus-mediated induction of decorin expression by endothelialcells contributes to tube formation and prevention of apoptosis in collagen lattices

Resting endothelial cells express the small proteoglycan biglycan, whereas sprouting endothelial cells also synthesize decorin, a related proteoglycan , Here we show that decorin is expressed in endothelial cells in human gran ulomatous tissue. For in vitro investigations, the human endothelium-derive d cell line, EA.hy 926, was cultured for 6 or more days in the presence of 1% fetal calf serum on top of or within floating collagen lattices which we re also populated by a small number of rat fibroblasts. Endothelial cells a ligned in cord-like structures and developed cavities that were surrounded by human decorin, About 14% and 20 % of endothelial cells became apoptotic after 6 and 12 days of co-culture, respectively. In the absence of fibrobla sts, however, the extent of apoptosis was about 60 % after 12 days, and cor d-like structures were not formed nor could decorin production be induced. This was also the case when lattices populated by EA.hy 926 cells were main tained under one of the Following conditions: 1) 10 % fetal calf serum; 2) fibroblast-conditioned media; 3) exogenous decorin; or 4) treatment with in dividual growth factors known to be involved in angiogenesis. The mechanism (s) by which fibroblasts induce an angiogenic phenotype in EA.hy 926 cells is (are) not known, but a causal relationship between decorin expression an d endothelial cell phenotype was suggested by transducing human decorin cDN A into EA.hy 926 cells using a replication-deficient adenovirus. When the t ransduced cells were cultured in collagen lattices, there was no requiremen t of fibroblasts for the formation of capillary-like structures and apoptos is was reduced. Thus. decorin expression seems to be of special importance for the survival of EA.hy 926 cells as well as for cord and tube formation in this angiogenesis model.