Induction of endothelial cell migration by proline analogs and its relevance to angiogenesis.
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.
McAuslan
B R
BR
CSIRO Division of Molecular Biology, North Ryde, NSW, Australia.
Reilly
W
W
Hannan
G N
GN
Schindhelm
K
K
Milthorpe
B
B
Saur
B A
BA
D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004343:Drug Implants; D004727:Endothelium / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006909:Hydroxyproline / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology
D001385:Azetines; D004343:Drug Implants; C002195:3,4-dehydroproline; D001383:Azetidinecarboxylic Acid; D004815:Epidermal Growth Factor; D003094:Collagen; D011392:Proline; D011393:Procollagen-Proline Dioxygenase; D006909:Hydroxyproline