Tsai I-Jung, Croft Kevin D, Mori Trevor A, Falck John R, Beilin Lawrence J, Puddey Ian B, Barden Anne E
University of Western Australia School of Medicine and Pharmacology, Royal Perth Hospital, Perth, WA 6000, Australia.
Free Radic Biol Med. 2009 Jan 15;46(2):263-70. doi: 10.1016/j.freeradbiomed.2008.10.028. Epub 2008 Nov 1.
20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that regulates vascular function and sodium homeostasis. Studies showing an association between 20-HETE excretion, raised BMI, and oxidative stress suggest that 20-HETE may be important in the development of cardiovascular disease in the metabolic syndrome (MetS). We investigated whether 20-HETE and F(2)-isoprostanes (markers of oxidative stress) were altered in the MetS before and after weight reduction. A case-controlled comparison of 30 participants with the MetS and matched controls showed that plasma and urinary 20-HETE and F(2)-isoprostanes were significantly elevated in the MetS group. There was a significant gender x group interaction such that women with the MetS had higher urinary 20-HETE and F(2)-isoprostanes compared to controls (p<0.0001). In a randomized controlled trial, 42 participants with the MetS were assigned to 16 weeks of weight maintenance or a 12-week weight-loss program followed by 4 weeks weight stabilization. Relative to the weight-maintenance group, a 4-kg loss in weight resulted in a 2-mm Hg fall in blood pressure (BP) but did not alter urinary or plasma 20-HETE or F(2)-isoprostanes. 20-HETE and oxidative stress may be important mediators of cardiovascular disease risk in the MetS. Although a 4% reduction in body weight reduced BP, there were no changes in plasma or urinary 20-HETE or F(2)-isoprostanes.
20-羟基二十碳四烯酸(20-HETE)是花生四烯酸的一种细胞色素P450代谢产物,可调节血管功能和钠稳态。研究表明20-HETE排泄、体重指数升高与氧化应激之间存在关联,提示20-HETE可能在代谢综合征(MetS)心血管疾病的发生发展中起重要作用。我们研究了在体重减轻前后,MetS患者体内的20-HETE和F(2)-异前列腺素(氧化应激标志物)是否发生改变。对30名MetS患者和匹配的对照组进行病例对照比较,结果显示MetS组的血浆和尿液中20-HETE及F(2)-异前列腺素显著升高。存在显著的性别×组间交互作用,即患有MetS的女性与对照组相比,尿液中的20-HETE和F(2)-异前列腺素水平更高(p<0.0001)。在一项随机对照试验中,42名MetS患者被分配到维持体重16周或进行为期12周的减肥计划,随后4周体重稳定阶段。相对于体重维持组,体重减轻4千克导致血压下降2毫米汞柱,但并未改变尿液或血浆中的20-HETE或F(2)-异前列腺素水平。20-HETE和氧化应激可能是MetS心血管疾病风险的重要介导因素。尽管体重降低4%可降低血压,但血浆或尿液中的20-HETE或F(2)-异前列腺素水平并无变化。