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

Citation
F. Cipollone et al., Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina, CIRCULATION, 102(9), 2000, pp. 1007-1013
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
102
Issue
9
Year of publication
2000
Pages
1007 - 1013
Database
ISI
SICI code
0009-7322(20000829)102:9<1007:OSAATB>2.0.ZU;2-O
Abstract
Background-Unstable angina is associated with enhanced lipid peroxidation a nd reduced antioxidant defenses. We have previously reported aspirin failur e in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesi s 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 enhanc ed in unstable angina and contributes to aspirin-insensitive TX biosynthesi s. 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 h ealthy subjects for the measurement of immunoreactive 8-iso-PCF2 alpha and 11-dehydro-TXB2. 8-Iso-PGF(2 alpha) excretion was significantly higher in p atients with unstable angina (339+/-122 pg/mg creatinine) than in matched p atients 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 exc retion (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 va riant 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, t hus excluding a role of ischemia per se in the induction of increased F-2-i soprostane production. Conclusions-These findings establish a putative biochemical link between in creased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of an tioxidants in this setting.