title: Effect of 15-lipoxygenase metabolites on angiogenesis: 15(S)-HPETE is angiostatic and 15(S)-HETE is angiogenic.
abstract: OBJECTIVE
  15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] are the products of arachidonic acid formed in the 15-lipoxygenase pathway. They have opposing effects on the inflammatory process. The present study was designed to examine the role of these metabolites on angiogenesis, which is critically associated with inflammatory conditions.
  
  
  METHODS
  Chick chorio-allantoic membrane (CAM), rat aortic rings and human umbilical vein endothelial cells (HUVECs) in culture were used to study the effect of 15(S)-HETE and 15(S)-HPETE on angiogenesis. Biochemical markers of angiogenesis were analysed by ELISA.
  
  
  RESULTS
  15(S)-HETE increased vessel density in chick CAM, induced sprouting in rat aortic rings and increased endothelial cell-cell contact and formation of tubular network-like structures in HUVECs. Furthermore, it up-regulated the expression of CD31, E-selectin and vascular endothelial growth factor (VEGF) in HUVECs, indicating its pro-angiogenic effect. 15(S)-HPETE, on the other hand, decreased vessel density in chick CAM, down-regulated the expression of E-selectin (<35 %), VEGF (<90 %) and CD31 (<50 %) and did not produce sprouting in aortic rings, suggesting an anti-angiogenic property. 15(S)-HETE-mediated up-regulation of CD 31 and VEGF was reversed by treatment with 15(S)-HPETE.
  
  
  CONCLUSIONS
  These results indicate the divergent effects of hydroxy and hydroperoxy products of 15-LOX on angiogenesis, highlighting the role of these products in the co-dependence of inflammation and angiogenesis.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581 Kerala, India.
authors.forename: Sasikumar J
authors.initials: SJ
authors.lastname: Soumya
authors.forename: Sheela
authors.initials: S
authors.lastname: Binu
authors.forename: A
authors.initials: A
authors.lastname: Helen
authors.forename: K
authors.initials: K
authors.lastname: Anil Kumar
authors.forename: P
authors.initials: P
authors.lastname: Reddanna
authors.forename: Perumana R
authors.initials: PR
authors.lastname: Sudhakaran
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase