Angiogenin was initially purified from serum-free media conditioned by growth of a human adenocarcinoma cell line HT-29 based on its ability to initiate vascularization in the chicken embryo chorioallantoic membrane. A number of other tumor, as well as normal, cell lines can also secrete Angiogenin. In addition, Angiogenin is present in normal human plasma at levels as high as 60 - 120 ng/mL. Unlike other angiogenic factors such as FGF, Angiogenin is neither mitogenic nor chemotactic for vascular endothelial cells in vitro. However, Angiogenin can stimulate capillary and umbilical vein endothelial cells to produce diacylglycerol and secrete prostacyclin by phospholipase activation. Angiogenin, absorbed on plastic, can also support endothelial and fibroblast cell adhesion and spreading.
Surprisingly, Angiogenin has been found to be a member of the ribonuclease superfamily with approximately 35% sequence similarity at the amino acid level with pancreatic RNase. Angiogenin exhibits ribonucleolytic activity that is distinctly different than that of pancreatic RNase A. The ribonucleolytic activity of Angiogenin toward most RNase A substrates is much lower than that of RNase A. Nevertheless, the ribonucleolytic activity of Angiogenin is essential to its angiogenic activity since inhibition of the Angiogenin RNase activity will also abolish angiogenesis activity. Similar to several members of the RNase superfamily, Angiogenin is a cytotoxic agent that can abolish cellular protein synthesis. It has been demonstrated that Angiogenin-dependent protein synthesis inhibition can be attributed to the function of Angiogenin as a cytotoxic tRNA-specific RNAase.
A cell-surface Angiogenin binding protein has been purified and characterized. Tryptic peptide mapping and sequence analysis indicate that this binding protein is a member of the actin family.
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