Induction of endothelial cell migration by proline analogs and its relevance to angiogenesis

• Published in: Experimental cell research Vol. 176; no. 2; p. 248
• Main Authors: McAuslan, B R, Reilly, W, Hannan, G N, Schindhelm, K, Milthorpe, B, Saur, B A
• Format: Journal Article
• Language: English
• Published: United States 01-06-1988
• Subjects: Animals; Azetidinecarboxylic Acid - pharmacology; Azetines - pharmacology; Cattle; Cell Division - drug effects; Cell Movement - drug effects; Cells, Cultured; Collagen - biosynthesis; Drug Implants; Endothelium - drug effects; Epidermal Growth Factor - pharmacology; Hydroxyproline - pharmacology; Neovascularization, Pathologic - chemically induced; Procollagen-Proline Dioxygenase - antagonists & inhibitors; Proline - analogs & derivatives; Proline - pharmacology
• DOI: 10.1016/0014-4827(88)90328-X
• ISSN: 0014-4827

The proline analogs cis-4-hydroxy-L-proline, 3,4-dehydro-L-proline, and 2-azetidinecarboxylic acid induced increases in the migration rate of retinal capillary endothelial cells, aortal endothelial cells, corneal endothelial cells, aortal smooth muscle cells, and retinal pericytes. cis-4-hydroxy-D-proline did not. The optimal concentration for migration induction by any of the active agents was approximately 10(-5) M. At higher concentrations (5 x 10(-4) M) migration was not induced or was inhibited. When tested by subcutaneous implant assays in rabbits, cis-4-hydroxy-L-proline and 2-azetidinecarboxylic acid consistently elicited a marked angiogenic response. Whereas these compounds are known to modulate collagen synthesis and secretion, the concentrations at which they are effective inducers of migration suggest that they may have a more specific target than general collagen synthesis.