12(S)-HETE is a mitogenic factor for microvascular endothelial cells: its potential role in angiogenesis.
12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid] is a lipoxygenase metabolite of arachidonic acid. Treatment of murine-lung-derived microvascular endothelial cells (CD clone 4) with exogenous 12(S)-HETE promoted wound healing of injured endothelial cell monolayers. 12(S)-HETE, in a time- and dose-dependent manner, enhanced the growth of CD clone 4 cells. Thymidine incorporation assays demonstrated that 12(S)-HETE increased the DNA synthesis by > 4 fold. In addition, normal endothelial cell growth stimulated by serum could be dose-dependently inhibited by a select 12-lipoxygenase inhibitor (BHPP), suggesting that 12(S)-HETE is a physiological mitogenic factor for microvascular endothelial cells.
Tang
D G
DG
Department of Radiation Oncology, Wayne State University, Detroit, MI 48202, USA.
Renaud
C
C
Stojakovic
S
S
Diglio
C A
CA
Porter
A
A
Honn
K V
KV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008833:Microcirculation; D008934:Mitogens / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D010590:Phalloidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011652:Pulmonary Circulation; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D006893:Hydroxyeicosatetraenoic Acids; D008934:Mitogens; C060047:4-(3-(biotinylaminohexamethylenaminocarbonyl)propanoylaminomethyl)-2-methyl-1,3-dithiolane-2-yl-(Ala(7))phalloidin; D010590:Phalloidine; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001710:Biotin; D004247:DNA; D013936:Thymidine