Human angiogenin is a 14-kDa plasma protein with angiogenic and ribonucleolytic 
activities. Angiogenin binds specifically to aortic smooth muscle cells, 
activates second messenger pathways, and inhibits their proliferation. Human and 
bovine aortic smooth muscle cells were used to study the internalization and 
intracellular fate of human angiogenin at 37 degrees C. Using a specific 
antibody against angiogenin, we found that the internalized native protein was 
localized in the perinuclear region at 30 min and then dispersed throughout the 
cytoplasm. In conditions favoring receptor-mediated endocytosis, internalization 
of iodinated angiogenin showed a first peak at 5 min and then further increased 
for up to 24 h. The half-life of the molecule, calculated as 12 h in chase 
experiments, could contribute to its intracellular accumulation. In cell 
extracts, in addition to the 14-kDa protein, a 8.7-kDa fragment was observed at 
24 h, and three fragments with molecular mass of 10.5, 8.7, and 6. 1 kDa were 
detected at 48 h. Our data point to a specific internalization and processing of 
human angiogenin by aortic smooth muscle cells.