Background:

Angiogenin (Ang), also known as ALS9, is a member of the ribonuclease superfamily. It exhibits both angiogenic and non-angiogenic activities and is involved in endothelial cell migration, proliferation and differentiation. Ang shares approximately 35% amino acid sequence identity with pancreatic RNase. Although Ang has the same general catalytic properties as RNase A, its activity differs markedly both in magnitude and in specificity (1). The enzymatic activity of Ang appears to be essential for biological activity: replacements of important active site residues invariably diminish ribonuclease and angiogenesis activities in parallel, and a substitution that increases enzymatic activity also enhances angiogenic potency (2). Like other members of the ribonuclease superfamily, Ang is a cytotoxic agent that can eliminate cellular protein synthesis. It causes inhibition of protein synthesis by functioning as a cytotoxic tRNA-specific RNase (3). Ang stimulates capillary and umbilical vein endothelial cells to produce diacylglycerol and secrete prostacyclin by phospholipase activation (4). It is produced by a variety of tumor and normal cell types. Cells that express Ang include vascular endothelial and smooth muscle cells, fibroblasts, normal colonic epithelium, normal peripheral blood lymphocytes, lung and colonic epithelial tumor cell lines, and primary gastrointestinal adenocarcinomas. Ang is also present in normal human plasma. Research findings suggest that Ang also has antimicrobial properties (5). Researchers have identified several Ang mutations that may increase the risk of developing amyotrophic lateral sclerosis (ALS) (6).