A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/557 (2006.01) A61K 31/16 (2006.01) A61K 31/17 (2006.01) A61K 31/202 (2006.01) A61K 31/325 (2006.01) A61K 31/558 (2006.01) A61K 38/44 (2006.01) A61K 45/06 (2006.01) A61P 29/00 (2006.01) C12Q 1/26 (2006.01) A61K 48/00 (2006.01)
Patent
CA 2390472
Epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases that have vasodilatory properties similar to endothelium-derived hyperpolarizing factor (EDHF). The cytochrome P450 isoform CYP2J2 was cloned and identified as a source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytolcine-induced endothelial cell adhesion molecule expression and prevented subsequent leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-.kappa.B and I.kappa.B kinase (IKK). The inhibitory effects of EETs were independent of their membrane hypopolarizing effects suggesting that these molecules play an important non-vasodilatory role in vascular inflammation.
L'invention concerne les acides époxyeicosatriénoïques (EET) qui sont des produits des époxygénases du cytochrome P450 ayant des propriétés de vasodilatation analogues au facteur hyperpolarisant dérivé de l'endothélium (EDHF). L'isoforme CYP2J2 du cytochrome P450, cloné, est identifié comme source des EET dans des cellules endothéliales humaines. Des concentrations physiologiques des EET ou une surexpression de CYP2J2 réduisent l'expression de la molécule d'adhésion cellulaire endothéliale induite par la cytokine, empêchant l'adhésion ultérieure de leucocytes à la paroi vasculaire par un mécanisme impliquant l'inhibition du facteur de transcription de kinase NF-.kappa.B et I.kappa.B (IKK). Les effets inhibiteurs des EET sont indépendants des effets hypopolarisants de leur membrane, ce qui laisse suggérer que ces molécules jouent un rôle de non vasodilatation important au niveau de l'inflammation vasculaire.
Liao James K.
Zeldin Darryl
Smart & Biggar
The Brigham And Women's Hospital Inc
The National Institute The Government Of The United States Of America As Represented By
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