Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3230-3235
© 1997 American Heart Association, Inc.
Articles |
In Vivo Formation of 8-Epi-Prostaglandin F2
Is Increased in Hypercholesterolemia
From the Departments of Medicine (G.D. A.M., F. Costantini, F. Cipollone), Pharmacology (C.P.), and Biochemistry (T.B.), University of Chieti "G. D'Annunzio" School of Medicine, Chieti; the Department of Pharmacology, Catholic University School of Medicine, Rome (G.M., G.C.); and the Division of Internal Medicine, Civil Hospital of Venice (P.A., G.B.B.), Italy.
Correspondence to Carlo Patrono, MD, Cattedra di Farmacologia I, Universita degli Studi "G. D'Annunzio," Via del Vestini 31, 66013 Chieti, Italy. E-mail cpatrono{at}unich.it
Abstract F2-isoprostanes are bioactive
prostaglandin (PG) -like compounds that are produced from
arachidonic acid through a nonenzymatic process of
lipid peroxidation catalyzed by oxygen free-radicals.
8-Epi-PGF2 may amplify the platelet
response to agonists, circulates in plasma, and is excreted in urine.
We examined the hypothesis that the formation of
8-epi-PGF2 is altered in patients with
hypercholesterolemia and contributes to
platelet activation in this setting. Urine samples were obtained
from 40 hypercholesterolemic patients and 40 age- and
sex-matched control subjects for measurement of immunoreactive
8-epi-PGF2. Urinary excretion of
11-dehydro-thromboxane (TX) B2, a major
metabolite of TXA2, was measured as an in vivo index of
platelet activation. Low-dose aspirin, indobufen, and vitamin E
were used to investigate the mechanism of formation and effects of
8-epi-PGF2 on platelet activation.
Urinary 8-epi-PGF2 was significantly
(P=.0001) higher in hypercholesterolemic
patients than in control subjects: 473±305 versus 205±95 pg/mg
creatinine. Its rate of excretion was inversely related to
the vitamin E content of LDL and showed a positive correlation with
urinary 11-dehydro-TXB2. Urinary
8-epi-PGF2 was unchanged after 2-week dosing
with aspirin and indobufen despite complete suppression of TX
metabolite excretion. Vitamin E supplementation was associated with
dose-dependent reductions in both urinary
8-epi-PGF2 and 11-dehydro-TXB2
by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively.
We conclude that the in vivo formation of the
F2-isoprostane 8-epi-PGF2 is
enhanced in the vast majority of patients with
hypercholesterolemia. This provides an
aspirin-insensitive mechanism possibly linking lipid peroxidation to
amplification of platelet activation in the setting of
hypercholesterolemia. Dose-dependent
suppression of enhanced 8-epi-PGF2 formation
by vitamin E supplementation may contribute to the beneficial effects
of antioxidant treatment.
Key Words: aspirin • F2-isoprostanes • thromboxane • hypercholesterolemia • vitamin E
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F. Cipollone, G. Ciabattoni, P. Patrignani, M. Pasquale, D. Di Gregorio, T. Bucciarelli, G. Davi, F. Cuccurullo, and C. Patrono Oxidant Stress and Aspirin-Insensitive Thromboxane Biosynthesis in Severe Unstable Angina Circulation, August 29, 2000; 102(9): 1007 - 1013. [Abstract] [Full Text] [PDF]
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O. Belton, D. Byrne, D. Kearney, A. Leahy, and D. J. Fitzgerald Cyclooxygenase-1 and -2-Dependent Prostacyclin Formation in Patients With Atherosclerosis Circulation, August 22, 2000; 102(8): 840 - 845. [Abstract] [Full Text] [PDF]
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B. Halliwell Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res, August 18, 2000; 47(3): 410 - 418. [Full Text] [PDF]
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A. Mezzetti, F. Cipollone, and F. Cuccurullo Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm Cardiovasc Res, August 18, 2000; 47(3): 475 - 488. [Abstract] [Full Text] [PDF]
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H. Wiseman, J. D O'Reilly, H. Adlercreutz, A. I Mallet, E. A Bowey, I. R Rowland, and T. A. Sanders Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans Am. J. Clinical Nutrition, August 1, 2000; 72(2): 395 - 400. [Abstract] [Full Text] [PDF]
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P. Patrignani, M. R. Panara, S. Tacconelli, F. Seta, T. Bucciarelli, G. Ciabattoni, P. Alessandrini, A. Mezzetti, G. Santini, M. G. Sciulli, et al. Effects of Vitamin E Supplementation on F2-Isoprostane and Thromboxane Biosynthesis in Healthy Cigarette Smokers Circulation, August 1, 2000; 102(5): 539 - 545. [Abstract] [Full Text] [PDF]
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E. Södergren, J. Cederberg, S. Basu, and B. Vessby Vitamin E Supplementation Decreases Basal Levels of F2-Isoprostanes and Prostaglandin F2{alpha} in Rats J. Nutr., January 1, 2000; 130(1): 10 - 14. [Abstract] [Full Text]
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C. Palombo, V. Lubrano, and T. Sampietro Oxidative stress, F2-isoprostanes and endothelial dysfunction in hypercholesterolemia Cardiovasc Res, December 1, 1999; 44(3): 474 - 476. [Full Text] [PDF]
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S. H. Wilson, P. J.M. Best, L. O. Lerman, D. R. Holmes Jr., D. M. Richardson, and A. Lerman Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2{alpha}, in experimental hypercholesterolemia Cardiovasc Res, December 1, 1999; 44(3): 601 - 607. [Abstract] [Full Text] [PDF]
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P. J. M. Best, L. O. Lerman, J. C. Romero, D. Richardson, D. R. Holmes Jr, and A. Lerman Coronary Endothelial Function Is Preserved With Chronic Endothelin Receptor Antagonism in Experimental Hypercholesterolemia In Vitro Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2769 - 2775. [Abstract] [Full Text] [PDF]
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P. Pignatelli, F. M. Pulcinelli, L. Lenti, P. P. Gazzaniga, and F. Violi Vitamin E Inhibits Collagen-Induced Platelet Activation by Blunting Hydrogen Peroxide Arterioscler. Thromb. Vasc. Biol., October 1, 1999; 19(10): 2542 - 2547. [Abstract] [Full Text] [PDF]
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 A. D. Watson, G. Subbanagounder, D. S. Welsbie, K. F. Faull, M. Navab, M. E. Jung, A. M. Fogelman, and J. A. Berliner Structural Identification of a Novel Pro-inflammatory Epoxyisoprostane Phospholipid in Mildly Oxidized Low Density Lipoprotein J. Biol. Chem., August 27, 1999; 274(35): 24787 - 24798. [Abstract] [Full Text] [PDF]
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M. Reza Mehrabi, C. Ekmekcioglu, F. Tatzber, A. Oguogho, R. Ullrich, A. Morgan, F. Tamaddon, M. Grimm, H. D Glogar, and H. Sinzinger The isoprostane, 8-epi-PGF2{alpha}, is accumulated in coronary arteries isolated from patients with coronary heart disease Cardiovasc Res, August 1, 1999; 43(2): 492 - 499. [Abstract] [Full Text] [PDF]
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R. BRIGELIUS-FLOHÉ and M. G. TRABER Vitamin E: function and metabolism FASEB J, July 1, 1999; 13(10): 1145 - 1155. [Abstract] [Full Text]
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A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]
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G. Davi, G. Ciabattoni, A. Consoli, A. Mezzetti, A. Falco, S. Santarone, E. Pennese, E. Vitacolonna, T. Bucciarelli, F. Costantini, et al. In Vivo Formation of 8-Iso-Prostaglandin F2{alpha} and Platelet Activation in Diabetes Mellitus : Effects of Improved Metabolic Control and Vitamin E Supplementation Circulation, January 19, 1999; 99(2): 224 - 229. [Abstract] [Full Text] [PDF]
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J. L. Witztum To E or Not To E—How Do We Tell? Circulation, December 22, 1998; 98(25): 2785 - 2787. [Full Text] [PDF]
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M. P. Reilly, D. Pratico, N. Delanty, G. DiMinno, E. Tremoli, D. Rader, S. Kapoor, J. Rokach, J. Lawson, and G. A. FitzGerald Increased Formation of Distinct F2 Isoprostanes in Hypercholesterolemia Circulation, December 22, 1998; 98(25): 2822 - 2828. [Abstract] [Full Text] [PDF]
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J. A. Lawson, H. Li, J. Rokach, M. Adiyaman, S.-W. Hwang, S. P. Khanapure, and G. A. FitzGerald Identification of Two Major F2 Isoprostanes, 8,12-Iso- and 5-epi-8,12-Iso-isoprostane F2alpha -VI, in Human Urine J. Biol. Chem., November 6, 1998; 273(45): 29295 - 29301. [Abstract] [Full Text] [PDF]
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G. Davi, M. Romano, A. Mezzetti, A. Procopio, S. Iacobelli, T. Antidormi, T. Bucciarelli, P. Alessandrini, F. Cuccurullo, and G. B. Bon Increased Levels of Soluble P-Selectin in Hypercholesterolemic Patients Circulation, March 17, 1998; 97(10): 953 - 957. [Abstract] [Full Text] [PDF]
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 M. A. Forgione, N. Weiss, S. Heydrick, A. Cap, E. S. Klings, C. Bierl, R. T. Eberhardt, H. W. Farber, and J. Loscalzo Cellular glutathione peroxidase deficiency and endothelial dysfunction Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1255 - H1261. [Abstract] [Full Text] [PDF]
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