XXXX disruption of endothelial cell anchorage is enhanced in collagen enriched matrices.

@entity71950 @entity397 @entity548 @entity63
UNASSIGNED: @entity548 is one of the most striking effects of bites by viper snakes resulting in fast @entity548 and @entity63 in affected tissues. Snake venom metalloproteinases (SVMPs) are responsible for hemorrhagic activity, but the mechanisms involved in SVMP-induced @entity548 are not entirely understood and the study of such mechanisms greatly depends on in  vivo experiments. In  vivo, hemorrhagic SVMPs accumulate on basement membrane (BM) of venules and capillary vessels allowing the hydrolysis of collagen IV with consequent weakness and @entity397 of capillary walls. These effects are not reproducible in  vitro with conventional endothelial cell cultures. In this study we used two-dimension (2D) or three-dimension (3D) cultures of HUVECs on matrigel and observed the same characteristics as in ex  vivo experiments: only the hemorrhagic toxin was able to localize on surfaces or internalize endothelial cells in 2D cultures or in the surface of tubules formed on 3D cultures. The contribution of matrigel, fibronectin and collagen matrices in @entity71950 -induced endothelial cell damage was then analyzed. Collagen and matrigel substrates enhanced the endothelial cell damage induced by @entity71950 allowing toxin binding to focal adhesions, disruption of stress fibers, detachment and apoptosis. The higher affinity of @entity71950 to collagen than to fibronectin explains the localization of the toxin within BM. Moreover, once located in BM, interactions of @entity71950 with a2b1 integrin would favor its localization on focal adhesions, as observed in our study. The accumulation of toxin in focal adhesions, observed only in cells grown in collagen matrices, would explain the enhancement of cell damage in these matrices and reflects the actual interaction among toxin, endothelial cells and BM components that occurs in  vivo and results in the @entity548 induced by viper venoms.
