title: Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina.
abstract: 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(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis.
  
  
  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-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha) 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(2alpha) was linearly correlated with 11-dehydro-TXB(2) 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(2alpha) 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.
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. D'Annunzio" School of Medicine, Chieti, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cipollone
authors.forename: G
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: P
authors.initials: P
authors.lastname: Patrignani
authors.forename: M
authors.initials: M
authors.lastname: Pasquale
authors.forename: D
authors.initials: D
authors.lastname: Di Gregorio
authors.forename: T
authors.initials: T
authors.lastname: Bucciarelli
authors.forename: G
authors.initials: G
authors.lastname: Davì
authors.forename: F
authors.initials: F
authors.lastname: Cuccurullo
authors.forename: C
authors.initials: C
authors.lastname: Patrono
mesh_terms: D000789:Angina, Unstable / Q000188:drug therapy* / Q000378:metabolism; D000975:Antioxidants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D028441:F2-Isoprostanes; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood; D013997:Time Factors
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; D007527:Isoenzymes; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; C075750:8-epi-prostaglandin F2alpha; D013928:Thromboxane A2; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin