Department of Surgery , Children 's Hospital , Boston , Massachusetts 02115 .
Exp Cell Res 212 : 262-73 ( 1994)
Abstract
The signal transduction pathways through which growth factors regulate vascular cell growth are not fully understood .
Recent studies suggest that metabolites of the lipoxygenase pathway may be involved in vascular cell growth .
We have measured the effect of the lipoxygenase pathway inhibitors nordihydroguiaretic acid ( NDGA ) , 5,6-dehydroarachidonic acid , and baicalein on bovine capillary endothelial cell ( EC ) and aortic smooth muscle cell ( SMC ) growth in the presence or the absence of growth factors .
NDGA totally suppressed serum-stimulated EC and SMC growth as well as growth factor-stimulated proliferation over a 9-day time course .
Removal of the inhibitor revealed that the inhibitory effect of NDGA was reversible and not due to cytotoxicity .
The morphology of NDGA-treated EC was changed in a reversible manner from the characteristic polygonal to spindle shape .
The 5-lipoxygenase inhibitor , 6-dehydroarachidonic acid had no effect on vascular cell proliferation , but inhibition of 12-lipoxygenase with baicalein blocked both EC and SMC cell growth in a dose-dependent manner , in the presence and the absence of growth factors .
Indomethacin , an inhibitor of the cyclooxygenase pathway , had no effect on EC and SMC proliferation .
Quinacrine and oleyloxyethylphosphorycholine inhibition of the phospholipase A2-catalyzed release of arachidonic acid from membrane phospholipids blocked growth factor- and serum-stimulated proliferation of EC and SMC .
These results suggested that arachidonic acid metabolites are critical intermediaries in the regulation of vascular cell growth .