EXPRESSION OF THROMBOSPONDINS BY ENDOTHELIAL-CELLS - INJURY IS CORRELATED WITH TSP-1

The thrombospondins (TSP-1, -2, and -3) comprise a family of proteins that are homologous at the carboxy terminus but have unique sequences at the amino terminus that might be correlated with the regulation of cell behavior. To investigate the expression of TSP-1, -2, and -3 in e ndothelial cells, we examined developing murine blood vessels and huma n atherosclerotic plaques by in situ hybridization. The expression of TSP-1 was also characterized in cultured bovine aortic endothelial cel ls. Expression of TSP-2 was seen in the dorsal aorta as early as embry onic day 10; TSP-1 tons not detected in endothelial cells until Inter stages, and TSP-3 tons not apparent in the vasculature, In atheroscler otic specimens, TSP-1 mRNA was detected in many intraplaque microvesse ls and in the endothelium lining the atheromatous plaque; TSP-2 was ab sent from these regions. Cultured bovine aortic endothelial cells did not transcribe TSP-2 mRNA at detectable levels. There were high steady -state levels of TSP-1 mRNA in subconfluent bovine aortic endothelial cells before confluence and at the wound edge after injury of the cell monolayer, with maximal expression of TSP-1 in cultures at a time dur ing which approximately 35% of the cells were in S phase. As the major ity of these cells subsequently undergo mitosis, these data are consis tent with TSP-1 as an inhibitor of endothelial cell proliferation that functions in GI. These results support the conclusion that, despite s equence homology, the TSPs have distinct functions in vascular biology .