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 meta bolite of arachidonic acid. Treatment of murine-lung-derived microvasc ular 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 c ells. Thymidine incorporation assays demonstrated that 12(S)-HETE incr eased the DNA synthesis by > 4 fold. In addition, normal endothelial c ell 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 cell s. (C) 1995 Academic Press, Inc.