15-Hydroxyeicosatetraenoic acid stimulates migration of human retinal microvessel endothelium in vitro and neovascularization in vivo.
We evaluated 15-hydroxyeicosatetraenoic acid (15-HETE), a major arachidonic acid product of vascular endothelium and leukocytes, for its effect on neovascularization. In a modified Boyden chamber assay, 15-HETE (10-7 M) stimulated human retinal microvessel endothelial cell migration by 42 +/- 10% (mean +/- S.E.M., p less than 0.01). 12-HETE, a major arachidonic acid metabolite of platelets, had no such effect. Further studies in the rabbit corneal pocket assay revealed that 15-HETE stimulated neovascularization in vivo. Concentrations at which the in vivo effects were observed are within the range generated by several cell types and are achievable in human serum. 15-HETE stimulation of human endothelial cell migration in vitro and neovascularization in vivo suggests that it may play a role in vasoproliferative disorders.
Division of Pediatrics and Ophthalmology, Johns Hopkins Hospital, Baltimore, Maryland 21205.
J E
JE
Graeber
B M
BM
Glaser
B N
BN
Setty
J A
JA
Jerdan
R W
RW
Walenga
M J
MJ
Stuart
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008833:Microcirculation / Q000502:physiology; D009389:Neovascularization, Pathologic; D011817:Rabbits; D012016:Reference Values; D012171:Retinal Vessels / Q000502:physiology*
D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid