From the Istituto di Fisiopatologia Medica (D.L., S. de G., G.C., A.M.,
F.C.), Istituto di Patologia Chirurgica (S.U., A.M.N.), Cattedra di
Cardiochirurgia (A.M.C.), and Istituto di Scienze Biochimiche (C. Di I.),
Universitá degli Studi "G. D'Annunzio,"
Facoltá di Medicina e Chirurgia, 66100 Chieti, Italy.
Correspondence to Domenico Lapenna, MD, c/o Presidenza Facoltá di Medicina e Chirurgia, Via dei Vestini, 66100 Chieti, Italy.
BackgroundOxidative stress,
resulting from an antioxidant/prooxidant imbalance, seems to be crucial
in atherogenesis. Recent evidence has emerged, however, of a
surprisingly high content of low-molecular-weight antioxidants in human
atherosclerotic plaques, although other antioxidant systems have not
been investigated in these lesions.
Methods and ResultsWe studied glutathione-related antioxidant
defenses (which play a key role in tissue antioxidant protection) in
carotid atherosclerotic plaques of 13 patients subjected to
endarterectomy and in normal internal mammary
arteries of 13 patients undergoing coronary artery bypass
surgery. Selenium-dependent glutathione peroxidase activity was
undetectable in the plaques of 7 patients; the other 6 patients with
plaques showed a mean enzymatic activity
ConclusionsA weak glutathione-related enzymatic antioxidant
shield is present in human atherosclerotic lesions. Although the
cause of this phenomenon remains to be determined, the present data
suggest that a specific antioxidant/prooxidant imbalance operative in
the vascular wall may be involved in atherogenic processes in humans.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Glutathione-Related Antioxidant Defenses in Human Atherosclerotic Plaques
3.5-fold lower than that of
mammary arteries. Glutathione reductase activity was also markedly
lower in the plaques than in the arteries. Glutathione transferase
instead had comparable activity in the two tissues. Remarkably, 5 of
the 7 patients with an undetectable selenium-dependent glutathione
peroxidase activity but none of the 6 with a detectable one were
characterized by multivascular atherosclerotic involvement (3 patients)
or stenosis of the contralateral carotid artery (2
patients).
Key Words: atherosclerosis antioxidants enzymes
This article has been cited by other articles:
![]() |
P. Giral, N. Jacob, C. Dourmap, B. Hansel, A. Carrie, E. Bruckert, X. Girerd, and M. J. Chapman Elevated Gamma-Glutamyltransferase Activity and Perturbed Thiol Profile Are Associated With Features of Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 587 - 593. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Qiao, M. Kisgati, J. M. Cholewa, W. Zhu, E. J. Smart, M. S. Sulistio, and R. Asmis Increased Expression of Glutathione Reductase in Macrophages Decreases Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1375 - 1382. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Musaad and E. N. Haynes Biomarkers of Obesity and Subsequent Cardiovascular Events Epidemiol. Rev., May 10, 2007; (2007) mxm005v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L.T. Ballard and J. M. Edelberg Stem Cells and the Regeneration of the Aging Cardiovascular System Circ. Res., April 27, 2007; 100(8): 1116 - 1127. [Abstract] [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] |
||||
![]() |
M. Torzewski, V. Ochsenhirt, A. L. Kleschyov, M. Oelze, A. Daiber, H. Li, H. Rossmann, S. Tsimikas, K. Reifenberg, F. Cheng, et al. Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 850 - 857. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. S. Mahadevan, M. Campbell, P. P. McKeown, and U. Bayraktutan Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity Cardiovasc Res, October 1, 2006; 72(1): 60 - 68. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Cao, H. Zhu, L. Zhang, X. Zhao, J. L. Zweier, and Y. Li Antioxidants and Phase 2 Enzymes in Cardiomyocytes: Chemical Inducibility and Chemoprotection Against Oxidant and Simulated Ischemia-Reperfusion Injury Experimental Biology and Medicine, September 1, 2006; 231(8): 1353 - 1364. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. de Haan, P. K. Witting, N. Stefanovic, J. Pete, M. Daskalakis, I. Kola, R. Stocker, and J. J. Smolich Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet J. Lipid Res., June 1, 2006; 47(6): 1157 - 1167. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Galasso, S. Schiekofer, K. Sato, R. Shibata, D. E. Handy, N. Ouchi, J. A. Leopold, J. Loscalzo, and K. Walsh Impaired Angiogenesis in Glutathione Peroxidase-1-Deficient Mice Is Associated With Endothelial Progenitor Cell Dysfunction Circ. Res., February 3, 2006; 98(2): 254 - 261. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Mayr, Y.-L. Chung, U. Mayr, X. Yin, L. Ly, H. Troy, S. Fredericks, Y. Hu, J. R. Griffiths, and Q. Xu Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2135 - 2142. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hamanishi, H. Furuta, H. Kato, A. Doi, M. Tamai, H. Shimomura, S. Sakagashira, M. Nishi, H. Sasaki, T. Sanke, et al. Functional Variants in the Glutathione Peroxidase-1 (GPx-1) Gene Are Associated With Increased Intima-Media Thickness of Carotid Arteries and Risk of Macrovascular Diseases in Japanese Type 2 Diabetic Patients Diabetes, September 1, 2004; 53(9): 2455 - 2460. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Blankenberg, H. J. Rupprecht, C. Bickel, M. Torzewski, G. Hafner, L. Tiret, M. Smieja, F. Cambien, J. Meyer, K. J. Lackner, et al. Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease N. Engl. J. Med., October 23, 2003; 349(17): 1605 - 1613. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A.C. 't Hoen, C. A.C. Van der Lans, M. Van Eck, M. K. Bijsterbosch, T. J.C. Van Berkel, and J. Twisk Aorta of ApoE-Deficient Mice Responds to Atherogenic Stimuli by a Prelesional Increase and Subsequent Decrease in the Expression of Antioxidant Enzymes Circ. Res., August 8, 2003; 93(3): 262 - 269. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Forgione, A. Cap, R. Liao, N. I. Moldovan, R. T. Eberhardt, C. C. Lim, J. Jones, P. J. Goldschmidt-Clermont, and J. Loscalzo Heterozygous Cellular Glutathione Peroxidase Deficiency in the Mouse: Abnormalities in Vascular and Cardiac Function and Structure Circulation, August 27, 2002; 106(9): 1154 - 1158. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Dimitrova, K. W. DeGroot, A. M. Pacquing, J. P. Suyderhoud, E. A. Pirovic, T. J. Munro, J. A. Wieneke, A. K. Myers, and Y. D. Kim Estradiol prevents homocysteine-induced endothelial injury in male rats Cardiovasc Res, February 15, 2002; 53(3): 589 - 596. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Trevisan, R. Browne, M. Ram, P. Muti, J. Freudenheim, A. M. Carosella, and D. Armstrong Correlates of Markers of Oxidative Status in the General Population Am. J. Epidemiol., August 15, 2001; 154(4): 348 - 356. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fischer, D. E Gutstein, Z. A Fayad, and V. Fuster Predicting plaque rupture: enhancing diagnosis and clinical decision-making in coronary artery disease Vascular Medicine, August 1, 2000; 5(3): 163 - 172. [Abstract] [PDF] |
||||
![]() |
M. H. WILSON, P. J. GRANT, L. J. HARDIE, and C. P. WILD Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction FASEB J, April 1, 2000; 14(5): 791 - 796. [Abstract] [Full Text] |
||||
![]() |
H. Drexler Nitric oxide and coronary endothelial dysfunction in humans Cardiovasc Res, August 15, 1999; 43(3): 572 - 579. [Full Text] [PDF] |
||||
![]() |
A. Prasad, N. P. Andrews, F. A. Padder, M. Husain, and A. A. Quyyumi Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability J. Am. Coll. Cardiol., August 1, 1999; 34(2): 507 - 514. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Gutstein and V. Fuster Pathophysiology and clinical significance of atherosclerotic plaque rupture Cardiovasc Res, February 1, 1999; 41(2): 323 - 333. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C.M. Siow, H. Sato, and G. E. Mann Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxide? Cardiovasc Res, February 1, 1999; 41(2): 385 - 394. [Abstract] [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1998 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |