Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin D C, Liao J K
Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, LMRC-322, Boston, MA 02115, USA.
Science. 1999 Aug 20;285(5431):1276-9. doi: 10.1126/science.285.5431.1276.
The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases that have vasodilatory properties similar to that of endothelium-derived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytokine-induced endothelial cell adhesion molecule expression, and EETs prevented leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-kappaB and IkappaB kinase. The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation.
环氧二十碳三烯酸(EETs)是细胞色素P450环氧化酶的产物,其具有与内皮衍生超极化因子相似的血管舒张特性。细胞色素P450同工酶CYP2J2被克隆并被鉴定为人类内皮细胞中EETs的潜在来源。EETs的生理浓度或CYP2J2的过表达降低了细胞因子诱导的内皮细胞黏附分子表达,并且EETs通过涉及抑制转录因子NF-κB和IκB激酶的机制阻止白细胞黏附于血管壁。EETs的抑制作用与其膜超极化作用无关,这表明这些分子在血管炎症中发挥重要的非血管舒张作用。