Control of capillary formation by membrane-anchored extracellular inhibitor of phospholipase A(2).
Secretory phospholipase A(2) (sPLA(2)) has been reported to be involved in cell proliferation in general and in endothelial cell migration, processes required for capillary formation. Subsequently, we examined the potential control of angiogenesis by sPLA(2) inhibition, using a cell-impermeable sPLA(2) inhibitor composed of N-derivatized phosphatidyl-ethanolamine linked to hyaluronic acid. This inhibitor effectively inhibits the proliferation and migration of human bone marrow endothelial cells in a dose-dependent manner, and suppresses capillary formation induced by growth factors involved in vascularization of tumors and of atherosclerotic plaques. It is proposed that sPLA(2) inhibition introduces a novel approach in the control of cancer development and atherosclerosis.
Chen
W M
WM
INSERM - EMI 99-12, Hôtel Dieu, Paris, France.
Soria
J
J
Soria
C
C
Krimsky
M
M
Yedgar
S
S
D002196:Capillaries / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010714:Phosphatidylethanolamines; D006820:Hyaluronic Acid; D010741:Phospholipases A