BACKGROUND AND AIMS: @entity6579 ( @entity15002 ) - a main component of oxidized LDL - is involved in @entity409 that precedes @entity731 , with an increased @entity224 anions and a reduced NO production via endothelial NO synthase (eNOS) uncoupling. However, there is no evidence about the mechanisms involved in neuronal NOS (nNOS) uncoupling. Extracellular signal-regulated kinase (ERK) is related to the control of NO production and inflammatory gene transcription activation in @entity731 . Our aim was to investigate the role of nNOS/ERK1/2 pathway on @entity409 induced by @entity15002 , in mouse aorta and human endothelial cells. METHODS: Thoracic aorta from wild type mice was used to perform vascular reactivity studies in the presence or absence of @entity15002 . Human endothelial cells were used to investigate the effect of @entity15002 on expression of nNOS and his products NO and @entity5568 . RESULTS: @entity15002 reduced @entity934 ( @entity3451 )-induced vasodilation in mouse aorta (EmaxCT/ @entity15002  =     95      2/62      3%, p  =  0.0004) and increased @entity2647 -induced vasoconstriction (EmaxCT/ @entity15002  =     4      0,1/6      0,1  mN/mm, p  =  0.0002), with a reduction in NO (fluorescence intensityCT/ @entity15002  =  91      3/62  2  *  10(3), p  =  0.0002) and @entity5568 (fluorescence intensityCT/ @entity15002  =     16      0,8/10      0,7  *  10(3), p  =  0.0041) production evocated by @entity3451 . An inhibition of nNOS by TRIM (EmaxCT/CT+TRIM  =     93      1/43      3%, p  =  0,0048; EmaxLPC/ @entity15002 +TRIM  =     62      3/65      3%) or @entity5568 degradation by catalase (EmaxCT/CT+cat  =     93      1/46      2%, p  <  0,001; EmaxLPC/ @entity15002 +cat  =     62,8      3,2/60,5      4,7%) reduced the relaxation in the control but not in @entity15002 group. @entity4286 , an ERK1/2 inhibitor, abolished the increase in vasoconstriction in @entity15002 -treated vessels (EmaxLPC/ @entity15002 +PD  =     6      0,1/3      0,1  mN/mm, p  =  0.0001). @entity15002 also reduced the dimer/monomer proportion and increased nNOS(ser852) phosphorylation. CONCLUSIONS: @entity15002 induced nNOS uncoupling and nNOS(Ser852) phosphorylation, reduced NO and @entity5568 production and improved @entity224 production by modulating ERK1/2 activity in human and murine endothelial cells.

Role of ERK1/2 activation and nNOS uncoupling on @entity409 induced by XXXX .

@entity5568 :: ('D006861', 'Chemical') :: ['H2O2'] @entity6579 :: ('MESH:D008244', 'Chemical') :: ['Lysophosphatidylcholine'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity409 :: ('MESH:D008107', 'Disease') :: ['endothelial dysfunction'] @entity2647 :: ('MESH:D010656', 'Chemical') :: ['phenylephrine'] @entity3451 :: ('D000109', 'Chemical') :: ['ACh'] @entity15002 :: ('CHEBI:16728', 'Chemical') :: ['LPC'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity6579 :: (MESH:D008244,Chemical) :: ['lysophosphatidylcholine']
