(Circulation. 1999;99:224-229.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
In Vivo Formation of 8-Iso-Prostaglandin F2
and Platelet Activation in Diabetes Mellitus
Effects of Improved Metabolic Control and Vitamin E Supplementation
From the Departments of Medicine and Aging (G.D., A.C., A.M., S.S., E.P., E.V., F. Costantini, F. Capani, C.P.) and Biomedical Sciences (T.B.), University of Chieti "G. D'Annunzio" School of Medicine; the Division of Internal Medicine, Civil Hospital of Popoli (A.F.); and the Department of Pharmacology (G.C.), Catholic University School of Medicine; Rome, Italy.
Correspondence to Dr Patrono, Department of Medicine and Aging, University of Chieti "G. D'Annunzio," via dei Vestini 31, 66013 Chieti, Italy. E-mail cpatrono{at}unich.it
Background—Diabetes mellitus
(DM) is associated with enhanced lipid peroxidation and persistent
platelet activation. We tested the hypothesis that the in vivo
formation of the F2-isoprostane
8-iso-prostaglandin (PG)F2
, a bioactive
product of arachidonic acid peroxidation, is
enhanced in DM and contributes to platelet activation.
Methods and Results—Urine samples were obtained from 85 diabetic
patients and 85 age- and sex-matched healthy subjects for measurement
of immunoreactive 8-iso-PGF2 and
11-dehydro-thromboxane B2 (TXM), an in vivo
index of platelet activation. Sixty-two had non–insulin-dependent
(NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E
supplementation, metabolic control, and
cyclooxygenase inhibitors were used to
investigate the mechanisms of formation of 8-iso-PGF2 in
this setting. Urinary 8-iso-PGF2 excretion was
significantly higher (P=0.0001) in NIDDM patients
(419±208 pg/mg creatinine; range 160 to 1014) than in
age-matched control subjects (208±92; 41 to 433). Urinary
8-iso-PGF2 was linearly correlated with blood glucose
and urinary TXM. 8-iso-PGF2 excretion was also
significantly (P=0.0001) higher in IDDM patients
(400±146; 183 to 702) than in control subjects (197±69; 95 to 353).
Vitamin E supplementation (600 mg/d for 14 days) was associated with a
statistically significant reduction in both urinary
8-iso-PGF2 (by 37%) and TXM (by 43%) in 10 NIDDM
patients. Improved metabolic control was associated with a
significant (P=0.0001) reduction in
8-iso-PGF2 and TXM excretion by 32% and 41%,
respectively, in 21 NIDDM patients. 8-iso-PGF2 was
unchanged after 2-week dosing with aspirin and indobufen despite
profound suppression of TXM excretion.
Conclusions—We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.
Key Words: diabetes mellitus • platelets • lipids • thromboxane • antioxidants
This article has been cited by other articles:
 |
|
 |
|
  G. L. Milne, H. Yin, and J. D. Morrow Human Biochemistry of the Isoprostane Pathway J. Biol. Chem., June 6, 2008; 283(23): 15533 - 15537. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Galle, E. Schwedhelm, S. Pinnetti, R. H. Boger, C. Wanner, and on behalf of the VIVALDI investigators Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy Nephrol. Dial. Transplant., May 1, 2008; (2008) gfn230v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bayat, S. Xu, D. Pimentel, R. A. Cohen, and B. Jiang Activation of Thromboxane Receptor Upregulates Interleukin (IL)-1 Induced VCAM-1 Expression Through JNK Signaling Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Davi and C. Patrono Platelet Activation and Atherothrombosis N. Engl. J. Med., December 13, 2007; 357(24): 2482 - 2494. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lewis, N. Stefanovic, J. Pete, A. C. Calkin, S. Giunti, V. Thallas-Bonke, K. A. Jandeleit-Dahm, T. J. Allen, I. Kola, M. E. Cooper, et al. Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice Circulation, April 24, 2007; 115(16): 2178 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I Avalos, C P Chung, A Oeser, G L Milne, J D Morrow, T Gebretsadik, A Shintani, C Yu, and C M Stein Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms Lupus, March 1, 2007; 16(3): 195 - 200. [Abstract] [PDF]
|
|
|
|
 |
|
 W. S. Waring, J. A. McKnight, D. J. Webb, and S. R.J. Maxwell Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers Diabetes, November 1, 2006; 55(11): 3127 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Watson Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Lipidomics: a global approach to lipid analysis in biological systems J. Lipid Res., October 1, 2006; 47(10): 2101 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Barani, I. Mattiasson, B. Lindblad, and A. Gottsater Cardiac Function, Inflammatory Mediators and Mortality in Critical Limb Ischemia Angiology, August 1, 2006; 57(4): 437 - 444. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Yasuda, S. Miyazaki, M. Kanda, Y. Goto, M. Suzuki, Y. Harano, and H. Nonogi Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase Eur. Heart J., May 2, 2006; 27(10): 1159 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Monnier, E. Mas, C. Ginet, F. Michel, L. Villon, J.-P. Cristol, and C. Colette Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes JAMA, April 12, 2006; 295(14): 1681 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Heistad Oxidative Stress and Vascular Disease: 2005 Duff Lecture Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. McGowan, S. R. Dunn, B. Falkner, and K. Sharma Stimulation of Urinary TGF-{beta} and Isoprostanes in Response to Hyperglycemia in Humans Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Stephens, D. R. Gable, S. J. Hurel, G. J. Miller, J. A. Cooper, and S. E. Humphries Increased Plasma Markers of Oxidative Stress Are Associated with Coronary Heart Disease in Males with Diabetes Mellitus and with 10-Year Risk in a Prospective Sample of Males Clin. Chem., March 1, 2006; 52(3): 446 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Santilli, G. Davi, A. Consoli, F. Cipollone, A. Mezzetti, A. Falco, T. Taraborelli, E. Devangelio, G. Ciabattoni, S. Basili, et al. Thromboxane-Dependent CD40 Ligand Release in Type 2 Diabetes Mellitus J. Am. Coll. Cardiol., January 17, 2006; 47(2): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Xu, B. Jiang, K. A. Maitland, H. Bayat, J. Gu, J. L. Nadler, S. Corda, G. Lavielle, T. J. Verbeuren, A. Zuccollo, et al. The Thromboxane Receptor Antagonist S18886 Attenuates Renal Oxidant Stress and Proteinuria in Diabetic Apolipoprotein E-Deficient Mice Diabetes, January 1, 2006; 55(1): 110 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Demiot, B. Fromy, J. L. Saumet, and D. Sigaudo-Roussel Preservation of pressure-induced cutaneous vasodilation by limiting oxidative stress in short-term diabetic mice Cardiovasc Res, January 1, 2006; 69(1): 245 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tang, T. Cyrus, Y. Yao, L. Vocun, and D. Pratico Involvement of Thromboxane Receptor in the Proatherogenic Effect of Isoprostane F2{alpha}-III: Evidence From Apolipoprotein E- and LDL Receptor-Deficient Mice Circulation, November 1, 2005; 112(18): 2867 - 2874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, May 1, 2005; 10(2_suppl): S97 - S102. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Santus, A. Sola, P. Carlucci, F. Fumagalli, A. Di Gennaro, M. Mondoni, C. Carnini, S. Centanni, and A. Sala Lipid Peroxidation and 5-Lipoxygenase Activity in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 838 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sanderson, J. Emery, T. Baglin, and A.-L. Kinmonth Narrative Review: Aspirin Resistance and Its Clinical Implications Ann Intern Med, March 1, 2005; 142(5): 370 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pagnin, G. Fadini, R. de Toni, A. Tiengo, L. Calo, and A. Avogaro Diabetes Induces p66shc Gene Expression in Human Peripheral Blood Mononuclear Cells: Relationship to Oxidative Stress J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1130 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Morrow Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 279 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Roberts and R. J. Barnard Effects of exercise and diet on chronic disease J Appl Physiol, January 1, 2005; 98(1): 3 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Young Oxidative Stress and Vascular Disease: Insights from Isoprostane Measurement Clin. Chem., January 1, 2005; 51(1): 14 - 15. [Full Text] [PDF]
|
|
|
|
|
|
N. R. Madamanchi, A. Vendrov, and M. S. Runge Oxidative Stress and Vascular Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Davi, M. Neri, A. Falco, D. Festi, T. Taraborelli, G. Ciabattoni, S. Basili, F. Cuccurullo, and C. Patrono Helicobacter Pylori Infection Causes Persistent Platelet Activation In Vivo Through Enhanced Lipid Peroxidation Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 246 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. MONTUSCHI, P. J. BARNES, and L. J. ROBERTS II Isoprostanes: markers and mediators of oxidative stress FASEB J, December 1, 2004; 18(15): 1791 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham, R. Rezzani, L. Rodella, A. Kruger, D. Taller, G. Li Volti, A. I. Goodman, and A. Kappas Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2468 - H2477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Krotz, H.-Y. Sohn, and U. Pohl Reactive Oxygen Species: Players in the Platelet Game Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1988 - 1996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Vincent, J. W. Russell, P. Low, and E. L. Feldman Oxidative Stress in the Pathogenesis of Diabetic Neuropathy Endocr. Rev., August 1, 2004; 25(4): 612 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-m. R. Wong, J. W. Stephens, J. Acharya, S. J. Hurel, S. E. Humphries, and P. J. Talmud The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease J. Lipid Res., August 1, 2004; 45(8): 1565 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yu, C. S. Ho, and C. W.K. Lam Biological Variation of Plasma F2-Isoprostane-III and Arachidonic Acid in Healthy Individuals Clin. Chem., August 1, 2004; 50(8): 1428 - 1430. [Full Text] [PDF]
|
|
|
|
|
|
J. Helmersson, B. Vessby, A. Larsson, and S. Basu Association of Type 2 Diabetes With Cyclooxygenase-Mediated Inflammation and Oxidative Stress in an Elderly Population Circulation, April 13, 2004; 109(14): 1729 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Schwedhelm, A. Bartling, H. Lenzen, D. Tsikas, R. Maas, J. Brummer, F.-M. Gutzki, J. Berger, J. C. Frolich, and R. H. Boger Urinary 8-iso-Prostaglandin F2{alpha} as a Risk Marker in Patients With Coronary Heart Disease: A Matched Case-Control Study Circulation, February 24, 2004; 109(7): 843 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fonseca, C. Desouza, S. Asnani, and I. Jialal Nontraditional Risk Factors for Cardiovascular Disease in Diabetes Endocr. Rev., February 1, 2004; 25(1): 153 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Minuz, P. Patrignani, S. Gaino, F. Seta, M. L. Capone, S. Tacconelli, M. Degan, G. Faccini, A. Fornasiero, G. Talamini, et al. Determinants of Platelet Activation in Human Essential Hypertension Hypertension, January 1, 2004; 43(1): 64 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett, J. F. Keaney Jr., and M. A. Creager Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2392 - H2398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E Upritchard, C. R. Schuurman, A. Wiersma, L. B. Tijburg, S. A. Coolen, P. J Rijken, and S. A Wiseman Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults Am. J. Clinical Nutrition, November 1, 2003; 78(5): 985 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Desideri, G. Croce, M. Tucci, G. Passacquale, S. Broccoletti, L. Valeri, A. Santucci, and C. Ferri Effects of Bezafibrate and Simvastatin on Endothelial Activation and Lipid Peroxidation in Hypercholesterolemia: Evidence of Different Vascular Protection by Different Lipid-Lowering Treatments J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5341 - 5347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling and G. A. FitzGerald Oxidative Stress and Cardiovascular Injury: Part II: Animal and Human Studies Circulation, October 28, 2003; 108(17): 2034 - 2040. [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, A. Zalewski, Y. Liu, T. Mazurek, S. Cowan, J. L. Martin, S. M. Hofmann, H. Vlassara, and Y. Shi Diabetes-Induced Oxidative Stress and Low-Grade Inflammation in Porcine Coronary Arteries Circulation, July 29, 2003; 108(4): 472 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Davi, F. Chiarelli, F. Santilli, M. Pomilio, S. Vigneri, A. Falco, S. Basili, G. Ciabattoni, and C. Patrono Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus: Role of Interleukin-6 and Disease Duration Circulation, July 1, 2003; 107(25): 3199 - 3203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Cracowski, J.-P. Baguet, P. Minuz, S. Gaino, M. Degan, L. Menapace, R. Tommasoli, G. Mansueto, E. Arosio, C. L. Santonastaso, et al. Isoprostanes: Are They More Than Physiopathological Biomarkers of Lipid Peroxidation? * Response Circulation, June 24, 2003; 107 (24): e222 - e222. [Full Text] [PDF]
|
|
|
|
|
|
L. Belhassen, G. Pelle, J.-L. Dubois-Rande, and S. Adnot Improved endothelial function by the thromboxane a2 receptor antagonist s 18886 in patients with coronary artery disease treated with aspirin J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Hoeldtke, K. D. Bryner, D. R. McNeill, S. S. Warehime, K. Van Dyke, and G. Hobbs Oxidative Stress and Insulin Requirements in Patients with Recent-Onset Type 1 Diabetes J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1624 - 1628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gresele, G. Guglielmini, M. De Angelis, S. Ciferri, M. Ciofetta, E. Falcinelli, C. Lalli, G. Ciabattoni, G. Davi, and G. B. Bolli Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Higdon and B. Frei Obesity and Oxidative Stress: A Direct Link to CVD? Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 365 - 367. [Full Text] [PDF]
|
|
|
|
|
|
J. F. Keaney Jr, M. G. Larson, R. S. Vasan, P. W.F. Wilson, I. Lipinska, D. Corey, J. M. Massaro, P. Sutherland, J. A. Vita, and E. J. Benjamin Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 434 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yano, N. Kitagawa, E. C. Gabazza, K. Morioka, H. Urakawa, T. Tanaka, A. Katsuki, R. Araki-Sasaki, Y. Hori, K. Nakatani, et al. Increased Plasma Thrombin-Activatable Fibrinolysis Inhibitor Levels in Normotensive Type 2 Diabetic Patients with Microalbuminuria J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 736 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. van Dam, V. W.M van Hinsbergh, C. D.A Stehouwer, A. Versteilen, H. Dekker, R. Buytenhek, H. M Princen, and C. G Schalkwijk Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects Cardiovasc Res, February 1, 2003; 57(2): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Cracowski, J.-P. Baguet, O. Ormezzano, J. Bessard, F. Stanke-Labesque, G. Bessard, and J.-M. Mallion Lipid Peroxidation Is Not Increased in Patients With Untreated Mild-to-Moderate Hypertension Hypertension, February 1, 2003; 41(2): 286 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sydow, E. Schwedhelm, N. Arakawa, S. M. Bode-Boger, D. Tsikas, B. Hornig, J. C. Frolich, and R. H. Boger ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins Cardiovasc Res, January 1, 2003; 57(1): 244 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|