Modulation of endothelial cell survival by an inhibitor of angiogenesis thrombospondin-1: a dynamic balance.

Angiogenesis is a process of capillary formation from pre-existing blood vessels. It is tightly controlled by the balance between positive and negative environmental signals--inducers and inhibitors of angiogenesis in such a way that predominance of inducers results in angiogenesis and predominance of inhibitors--in vascular quiescence. Here we discuss the ability of the angiogenic stimuli to promote survival and the pathways they may utilize. We also summarize information available on the signaling events elicited in the endothelial cells by a naturally occurring inhibitor of angiogenesis Thrombospondin-1 (TSP-1), that result in the endothelial cell apoptosis and inhibition of angiogenesis in vivo. This ability to cause programmed cell death in vascular endothelium is not unique to TSP-1. A substantial number of known angiogenesis inhibitors can also trigger apoptosis in the activated endothelial cells. This fact argues for the possibility of apoptosis to be a common denominator for a major fraction of anti-angiogenic molecules. If this is the case, it is equally possible that the ratio between environmental factors that control angiogenesis is interpreted within individual endothelial cell as a balance between pro-apoptotic and survival signals. Thus the relative strength of the death and survival signal or signals determines the fate of endothelial cell and therefore the fate of remodeling vessel.