Background: It has been well documented that free radical injury is involved in the progression of chronic renal failure. Extracellular superoxide dismutase (EC-SOD), localized on the endothelial cell surface, plays an important role in reducing oxidative stress especially in the vessels by binding to the endothelial cell surface via the heparin-binding domain. Although EC-SOD Arg213Gly, which cannot bind on endothelial cells, has been considered a polymorphism, the effect of EC-SOD on hemodialysis patients has not been well examined. Methods: In 178 hemodialysis patients, the following examinations were performed. EC-SOD Arg213Gly was examined by polymerase chain reaction (PCR)-induced mutation restriction analysis (PCR-IMRA). As indexes of atherosclerosis, the annual progression in intima-media thickness (ΔIMT), plaque score, pulse wave velocity (PWV) and plasma-oxidized low-density lipoprotein (OxLDL) values were examined. Results: PCR-IMRA revealed that 20 of 178 patients possessed the mutation (11.2%), and the incidence was about twice as high as that in a previously reported Japanese population. Although there were no statistical differences in plaque score and PWV with and without EC-SOD Arg213Gly, ΔIMT and plasma OxLDL values in patients with EC-SOD Arg213Gly were significantly higher than those in patients without the mutation. Conclusion: EC-SOD Arg213Gly is an accelerating factor for the progression of renal failure and atherosclerosis.

1.
Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C: Oxidative stress in end-stage renal disease: An emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272–1280.
2.
Schaur RJ: Basic aspects of the biochemical reactivity of 4-hydroxynonenal. Mol Aspects Med 2003;24:149–159.
3.
Witztum JL, Steinberg D: Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785–1792.
4.
Ross R: Atherosclerosis – An inflammatory disease. N Engl J Med 1999;340:115–126.
5.
Drueke TB, Khoa TN, Massy ZA, Witko-Sarsat V, Lacour B, Descamps-Latscha B: Role of oxidized low-density lipoprotein in the atherosclerosis of uremia. Kidney Int Suppl 2001;78:S114–S119.
6.
Steinbrecher UP, Parthasarathy S, Leake DS, et al: Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 1984;81:3883–3887.
7.
Carew TE, Schwenke DC, Steinberg D: Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: Evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of hyperlipidemic rabbit. Proc Natl Acad Sci USA 1987;84:7725–7729.
8.
Marklund SL: Extracellular superoxide dismutase and superoxide dismutase isozymes in tissues from nine mammalian species. Biochem J 1984;222:649–655.
9.
Marklund SL: Extracellular superoxide dismutase in human tissues and human cell lines. J Clin Invest 1984;74:1398–1403.
10.
Karlsson K, Lindahl U, Marklund SL: Binding of human extracellular superoxide dismutase C to sulphated glycosaminoglycans. Biochem J 1988;256:29–33.
11.
Adachi T, Marklund SL: Interactions between human extracellular superoxide dismutase C and sulfated polysaccharides. J Biol Chem 1989;264:8537–8541.
12.
Laukkanen MO, Lehtolainen P, Turunen P, et al: Rabbit extracellular superoxide dismutase: Expression and effect on LDL oxidation. Gene 2000;254:173–179.
13.
Sandström J, Nilsson P, Karlsson K, et al: 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. J Biol Chem 1994;269:19163–19166.
14.
Sasaki J, Cottam GL: Measurement of receptor-independent metabolism of low-density lipoprotein-an application of glycosylated low-density lipoprotein. Eur J Biochem 1983;13:535–538.
15.
Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986.
16.
Solymoss BV, Marcil M, Chaour M, et al: Fasting hyperinsulinism, insulin resistance syndrome, and coronary artery disease in men and women. Am J Cardiol 1995;76:1152–1156.
17.
Drueke TB: The pathogenesis of parathyroid gland hyperplasia in chronic renal failure. Kidney Int 1995;48:259–272.
18.
Itabe H, Yamamoto H, Imanaka T, et al: Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody. J Lipid Res 1996;37:45–53.
19.
Yasaka M, Omae T, Tsuchiya T, et al: Ultrasonic evaluation of the site of carotid axis occlusion in patients with acute cardioembolic stroke. Stroke 1992;23:420–422.
20.
Salonen JT, Salonen R: Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 1991;11:1245–1249.
21.
Avolio AP, Chen S, Wang R, Zhang C, Li M, O’Rourke MF: Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 1983;68:50–58.
22.
Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac A-M, Target R, Levy BI: Assessment of arterial distensibility by automatic pulse wave velocity measurement: Validation and clinical application study. Hypertension 1995;26:485–490.
23.
Lindner A, Charra B, Sherrard DJ, Scribner BH: Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697–701.
24.
Stralin P, Karlsson K, Johansson BO, et al: The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arierioscler Thromb Vasc Biol 1995;15:2032–2036.
25.
Yamada H, Yamada Y, Adachi T, et al: Molecular analysis of extracellular-superoxide dismutase gene associated with high level in serum. Jpn J Hum Genet 1995;40:177–184.
26.
Takatsu H, Tasaki H, Kim H-N, et al: Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation. Biochem Biophys Res Commun 2001;285:84–91.
27.
Maggi E, Bellazzi R, Gazo A, Seccia M, Bellomo G: Autoantibodies against oxidatively-modified LDL in uremic patients undergoing dialysis. Kidney Int 1994;46:869–876.
28.
van den Akker JM, Bredie SJ, Diepenveen SH, van Tits LJ, Stalenhoef AF, van Leusen R: Atorvastatin and simvastatin in patients on hemodialysis: Effects on lipoproteins, C-reactive protein and in vivo oxidized LDL. J Nephrol 2003;16:238–244.
29.
Kawagishi T, Nishizawa Y, Konishi T, et al: High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia. Kidney Int 1995;48:820–826.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.