Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 1998;97:1930-1934

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lapenna, D.
Right arrow Articles by Cuccurullo, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lapenna, D.
Right arrow Articles by Cuccurullo, F.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

(Circulation. 1998;97:1930-1934.)
© 1998 American Heart Association, Inc.


Clinical Investigation and Reports

Glutathione-Related Antioxidant Defenses in Human Atherosclerotic Plaques

Domenico Lapenna, MD; Sergio de Gioia, MD; Giuliano Ciofani, Tch; Andrea Mezzetti, MD; Sante Ucchino, MD; Antonio M. Calafiore, MD; Antonio M. Napolitano, MD; Carmine Di Ilio, PhD; ; Franco Cuccurullo, MD

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.

Background—Oxidative 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 Results—We 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 {approx}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).

Conclusions—A 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.


Key Words: atherosclerosis • antioxidants • enzymes




This article has been cited by other articles:


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
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]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
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]


Home page
Epidemiol RevHome page
S. Musaad and E. N. Haynes
Biomarkers of Obesity and Subsequent Cardiovascular Events
Epidemiol. Rev., May 10, 2007; (2007) mxm005v1.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
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]


Home page
CirculationHome page
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]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
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]


Home page
Cardiovasc ResHome page
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]


Home page
Exp. Biol. Med.Home page
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]


Home page
J. Lipid Res.Home page
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]


Home page
Circ. Res.Home page
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]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
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]


Home page
Physiol. Rev.Home page
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]


Home page
DiabetesHome page
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]


Home page
NEJMHome page
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]


Home page
Circ. Res.Home page
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]


Home page
CirculationHome page
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]


Home page
Cardiovasc ResHome page
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]


Home page
Am J EpidemiolHome page
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]


Home page
Vasc MedHome page
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]


Home page
FASEB J.Home page
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]


Home page
Cardiovasc ResHome page
H. Drexler
Nitric oxide and coronary endothelial dysfunction in humans
Cardiovasc Res, August 15, 1999; 43(3): 572 - 579.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
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]


Home page
Cardiovasc ResHome page
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]


Home page
Cardiovasc ResHome page
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]