Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina

被引:186
作者
Cipollone, F
Ciabattoni, G
Patrignani, P
Pasquale, M
Di Gregorio, D
Bucciarelli, T
Davì, G
Cuccurullo, F
Patrono, C
机构
[1] Univ Chieti G DAnnunzio, Sch Med, Dept Med & Aging, Chieti, Italy
[2] Univ Chieti G DAnnunzio, Sch Med, Dept Biomed Sci, Chieti, Italy
[3] Catholic Univ Rome, Sch Med, Dept Pharmacol, Rome, Italy
[4] F Renzetti Hosp, Div Cardiol, Lanciano, Italy
关键词
angina; aspirin; isoprostanes; thromboxane; oxidant stress;
D O I
10.1161/01.CIR.102.9.1007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F-2-isoprostane 8-iso-prostaglandin (PG)F-2 alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis. Methods and Results-Urine samples were obtained from patients with unstable angina (n=32), stable angina (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement of immunoreactive 8-iso-PCF2 alpha and 11-dehydro-TXB2. 8-Iso-PGF(2 alpha) excretion was significantly higher in patients with unstable angina (339+/-122 pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg creatinine. P=0.001) and control subjects (192+/-71 pg/mg creatinine, P<0.0001). In patients with unstable angina, 8-iso-PGF(2 alpha) was linearly correlated with 11-dehydro-TXB2 excretion (rho=0.721, P<0.0001) and inversely correlated with plasma vitamin E (rho=-0.710, P=0.004). Spontaneous myocardial ischemia in patients with variant angina or ischemia elicited by a stress test in patients with stable angina was not accompanied by any change in 8-iso-PGF(2 alpha) excretion, thus excluding a role of ischemia per se in the induction of increased F-2-isoprostane production. Conclusions-These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.
引用
收藏
页码:1007 / 1013
页数:7
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