Epoxyeicosatrienoic acid (EET)-stimulated angiogenesis is mediated by epoxy hydroxyeicosatrienoic acids (EHETs) formed from COX-2

Epoxyeicosatrienoic acids (EETs) are formed from the metabolism of arachidonic acid by cytochrome P450s. EETs promote angiogenesis linked to tumor growth in various cancer models that is attenuated in vivo by cyclooxygenase 2 (COX-2) inhibitors. This study further defines a role for COX-2 in mediating endothelial EET metabolism promoting angiogenesis. Using human aortic endothelial cells (HAECs), we quantified 8,9-EET-induced tube formation and cell migration as indicators of angiogenic potential in the presence and absence of a COX-2 inducer [phorbol 12,13-dibutyrate (PDBu)]. The angiogenic response to 8,9-EET in the presence of PDBu was 3-fold that elicited by 8,9-EET stabilized with a soluble epoxide hydrolase inhibitor (t-TUCB). Contributing to this response was the COX-2 metabolite of 8,9-EET, the 11-hydroxy-8,9-EET (8,9,11-EHET), which exogenously enhanced angiogenic responses in HAECs at levels comparable to those elicited by vascular endothelial growth factor (VEGF). In contrast, the 15-hydroxy-8,9-EET isomer was also formed but inactive. The 8,9,11-EHET also promoted expression of the VEGF family of tyrosine kinase receptors. These results indicate that 8,9-EET-stimulated angiogenesis is enhanced by COX-2 metabolism in the endothelium through the formation of 8,9,11-EHET. This alternative pathway for the metabolism of 8,9-EET may be particularly important in regulating angiogenesis under circumstances in which COX-2 is induced, such as in cancer tumor growth and inflammation

Avaliação de genótipos de Leucaena spp. nas condições edafoclimáticas de São Carlos, SP: I. caracterização fenotípica e avaliação agronômica Evaluation of Leucaena spp. genotypes in the edaphic and climatic conditions of São Carlos, SP: I. phenotypical characterization and agronomical evaluation

Para avaliar genótipos promissores de Leucaena spp., foi instalado experimento em Latossolo Vermelho-Amarelo distrófico, na área da EMBRAPA-CPPSE em São Carlos, situada a 22&deg;01'S e 47&deg;53'W, com altitude de 856 m e média de precipitação anual de 1502 mm. Foram testados os seguintes genótipos: Leucaena leucocephala cv. Texas 1074 (T1), L.leucocephala 29 A9 (T2), L.leucocephala 11 x L.diversifolia 25 (T3), L.leucocephala 11 x L.leucocephala 26 (T4), L.leucocephala 24-19/2-39 X L.diversifolia 26 (T5) e L.leucocephala cv. Cunningham (testemunha). Através das avaliações efetuadas durante o período de estabelecimento (15 meses), verificou-se que: a) as plantas de L.leucocephala 24-19/2-39 x L.diversifolia 26 se mostraram mais ramificadas e com maior produção de sementes; b) as plantas de L.leucocephala 11 x L.diversifolia 26 apresentaram a maior produção de matéria seca consumível; c) os materiais apresentaram brotação após o corte, semelhante ou inferior à testemunha.<br>To test promising genotypes of Leucaena spp., selected in a breeding program, an experiment was conducted in a distrofic Red-Yellow Latossol, at the experimental station of EMBRAPA/CPPSE, São Carlos,SP, located at 22&deg;01' and 47&deg;53'W, altitude of 856 m and with a mean annual precipitation of 1502 mm. The following genotypes were tested: L.leucocephala cv. Texas 1074 (T1), L.leucocephala 29 A9 (T2), L.leucocephala 11 x L.diversifolia 25 (T3), L.leucocephala 11 x L.diversifolia 26 (T4), L.leucocephala 24-19/2-39 x L.diversifolia 26 (T5) and L.leucocephala cv. Cunningham (control). Evaluations were performed during the establishment period (fifteen months) and it was concluded that: a) the plants of L.leucocephala 24-19/2-39 x L.diversifolia 26, with early flowering, were the most branched and presented the greatest seed yield; b) the plants of L.leucocephala 11 x L.diversifolia 26, showed the greatest edible dry matter yield; c) the genotypes presented similar or worse growth, than the control, after each harvest