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12(S)-HETE is a mitogenic factor for microvascular endothelial cells: its potential role in angiogenesis
D G Tang1, C Renaud, S Stojakovic
1Department of Radiation Oncology, Wayne State University, Detroit, MI 48202, USA.
Abstract:
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.