This Article Abstract Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strålin, P. Articles by Marklund, S. L. Search for Related Content PubMed PubMed Citation Articles by Strålin, P. Articles by Marklund, S. L. Pubmed/NCBI databases Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2032-2036.)
© 1995 American Heart Association, Inc.

Articles

The Interstitium of the Human Arterial Wall Contains Very Large Amounts of Extracellular Superoxide Dismutase

Pontus Strålin; Kurt Karlsson; Bengt O. Johansson; Stefan L. Marklund

From the Department of Clinical Chemistry (P.S., K.K., S.L.M.) and the Department of Anatomy (B.O.J.), Umeå University Hospital, Sweden.

Correspondence to Stefan L. Marklund, Department of Clinical Chemistry, Umeå University Hospital, S-901 85 Umeå, Sweden.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Abstract The levels of the secreted, interstitially located extracellular superoxide dismutase (EC-SOD), the cytosolic copper-and-zinc–containing SOD (CuZn-SOD), and the mitochondrial manganese-containing SOD (Mn-SOD) were measured in the walls of human coronary arteries, proximal thoracic aortas, and saphenous veins. The blood vessel walls, particularly the arteries, were found to contain exceptionally large amounts of EC-SOD, whereas the levels of CuZn-SOD and Mn-SOD were relatively low compared with other tissues. Analysis of EC-SOD by immunohistochemistry indicates an even distribution in the vessel wall, including large amounts in the arterial intima. Arterial smooth muscle cells were found to secrete large amounts of EC-SOD and likely are the principal source of the enzyme in the vascular wall. The EC-SOD concentration in the human arterial wall extracellular space is high enough to efficiently suppress the putative pathological effects of the superoxide radical, such as oxidation of LDL and reaction with nitric oxide to form the deleterious peroxynitrite. The levels of EC-SOD in the aortic wall are found to vary widely among species and were on average 6440 U/g in humans, 4340 U/g in the cow, 2660 U/g in the pig, 160 U/g in the dog, 770 U/g in the cat, 2390 U/g in the rabbit, 90 U/g in the rat, and 3400 U/g in the mouse. There were only moderate differences in the amounts of CuZn-SOD and Mn-SOD. This wide variation in EC-SOD content suggests that the susceptibility to pathologies induced by superoxide radicals in the vascular wall interstitium should vary widely among species.

Key Words: superoxide • nitric oxide • oxygen free radicals • atherosclerosis • LDL

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The effects of the superoxide radical and derived products on blood vessel functions have attracted increasing recent attention. Direct damaging effects on the endothelium¹ and other vessel components, involvement in the oxidation of LDL^{2 3 4 5} and hence potential involvement in atherosclerosis, noxious interactions with NO·,^{6 7 8 9 10} and direct effects on vessel tonus¹¹ have all been reported. However, despite the potential importance of the superoxide radical, little is known about the endogenous protection of the extracellular space and cells of the vascular wall provided by SODs.

To assess the role of SODs in blood vessel homeostasis we undertook the present study, in which we determined in human coronary artery, aorta, and saphenous vein the contents of the three SOD isoenzymes: the secreted EC-SOD,¹² the cytosolic CuZn-SOD,¹³ and the mitochondrial matrix Mn-SOD.¹⁴ We find comparatively little CuZn-SOD and Mn-SOD but exceptionally large amounts of EC-SOD. For comparison, we also measured the SOD isoenzymes in the aortas of a number of other mammalian species and found considerable interspecies variation in EC-SOD content.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Extraction of the Vessel Wall
Macroscopically normal pieces (0.5 to 1.5 g) of human LAD, proximal thoracic aorta, and saphenous vein were cut out at autopsy within 48 hours after death. Thoracic aortas from the other mammals were collected within a few hours after death. The pieces were kept at -80°C before analysis. For extraction, frozen pieces were pulverized in a Braun Microdismembrator II (B Brown Biotech Inc), and the frozen powder was added to 10 vol of 50 mmol/L potassium phosphate, pH 7.4, with 0.3 mol/L KBr and a set of antiproteolytic agents (0.5 mmol/L PMSF, 3 mmol/L DTPA , 90 mg/L aprotinin, 10 mg/L pepstatin, 10 mg/L chymostatin, and 10 mg/L leupeptin). The homogenates were then sonicated and finally extracted for 30 minutes at 4°C. The extracts were centrifuged (20 000g for 15 minutes). Unless analyzed immediately, the supernatants were stored at -80°C.

SOD Activity Analysis
SOD enzymatic activity was determined by the direct spectrophotometric method, employing KO₂¹⁵ as modified.¹⁶ To distinguish between the cyanide-sensitive isoenzymes CuZn-SOD and EC-SOD and the resistant Mn-SOD, 3 mmol/L cyanide was used. One unit in the assay is defined as the activity that brings about a decay of O₂^-· concentration at a rate of 0.1 s^-1 in 3 mL of buffer. It corresponds to 8.3 ng human CuZn-SOD, 6.3 ng bovine CuZn-SOD, 8.6 ng human EC-SOD, and 65 ng bovine Mn-SOD. The "KO₂ assay" is carried out at pH 9.5 and at a relatively high superoxide concentration. In comparison, the xanthine oxidase–cytochrome C SOD assay¹³ is carried out under more physiological conditions, ie, neutral pH and low superoxide concentration. One unit in the KO₂ assay corresponds to about 0.024 units CuZn-SOD and EC-SOD and 0.24 units Mn-SOD in the xanthine oxidase assay. The KO₂ assay is thus 10 times more sensitive for CuZn-SOD and EC-SOD activity than for Mn-SOD activity. The results presented in the tables were not corrected for this effect.

Specific Analysis of EC-SOD
EC-SOD in human blood vessel wall extracts was determined by ELISA.¹⁷ There is no cross-reactivity with human CuZn-SOD. For conversion of results to activity units, 8.6 ng per unit was assumed.¹⁸

For the specific analysis of EC-SOD in vessel extracts from other species, chromatography on Con A–Sepharose (Pharmacia Biotech) was used. Unlike CuZn-SOD and Mn-SOD, the glycoprotein EC-SOD binds to the lectin concanavalin A. The procedure has been described previously,¹⁹ the only difference being that the extraction buffer described above was used as a solvent in all steps. The yield of EC-SOD in the procedure was tested with human blood vessel extracts. Seventy-five percent of the applied EC-SOD was found to be recovered as determined by ELISA, and all EC-SOD results for the other mammals were corrected accordingly. The CuZn-SOD activity of the extracts was then calculated as total cyanide-sensitive SOD activity minus (corrected) EC-SOD activity.

Protein and DNA Analysis
For protein analysis, Coomassie brilliant blue G-250 was employed,²⁰ standardized with human serum albumin. DNA concentration was determined with fluorimetry as a complex with bisbenzimidazole (Hoechst 33258)²¹ using calf thymus DNA as a standard.

Effect of Storage on SOD Activity
Since the human samples were collected from bodies stored under refrigeration up to 48 hours, the effects of storage on the various analyzed factors were determined. Small pieces (around 300 mg) of cow aorta, prepared under aseptic conditions, were stored in 1.5-mL capped tubes in a refrigerator at 5°C. Tubes were transferred to -80°C at 1.5 hours, 12 hours, 24 hours, and daily up to 6 days after death. Three 1.5-hour samples and two from the other storage times were then homogenized and analyzed as described above for the animal samples. There were no systematic increases or decreases in the activities of the SOD isoenzymes or the contents of protein or DNA in the daily samples over the 6-day period. The means of the parameters in the two pieces stored at 5°C for 6 days deviated at most 13% from the means of the pieces stored for only 1.5 hours.

Immunohistochemistry
Vessels for immunostaining (LAD, thoracic aorta, and saphenous vein) were obtained at autopsy within 48 hours of death or immediately during vessel surgery. Cryostat sections were fixed for 45 minutes in a 1% paraformaldehyde solution. An avidin–biotin–horseradish peroxidase system (Dakopatts) was used for immunostaining. Anti-EC-SOD antibodies, raised against recombinant human protein¹⁸ in goat and rabbit and purified by adsorption/desorption on EC-SOD immobilized on CNBr-activated Sepharose, were used at concentrations of 0.7 to 8.6 mg/L. As negative controls, primary antibodies were substituted with nonimmunized goat/rabbit IgG (2.4 to 11.6 mg/L).

Cell Culture
The arterial smooth muscle cell lines were initiated from pieces of human uterine artery as described by Fager et al.²² Their identity as smooth muscle cells was assessed by morphological appearance and by their expression of smooth muscle -actin²³ (Boehringer Mannheim GmbH), and analyzed by flow cytometry. The cells were maintained in Waymouth MB 752/1 medium containing 15% fetal calf serum, 10⁵ U/L benzylpenicillin, 100 mg/L streptomycin, 2 mmol/L glutamine, and 1 mmol/L sodium pyruvate and were studied between the fifth and eighth passages.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Human Blood Vessel Walls
Human blood vessel walls, particularly the arteries, were found to contain exceptionally large amounts of EC-SOD, 10-fold more than average human tissues (Table 1). The levels of CuZn-SOD and Mn-SOD, on the other hand, were lower than in most other tissues. While in most tissues EC-SOD accounts for only a small percentage of the total SOD activity, the fraction in the arterial wall approaches 50%.

View this table: [in this window] [in a new window]   Table 1. Levels of SOD Isoenzymes in Human Blood Vessel Walls

Localization of EC-SOD by Immunohistochemistry
The distribution of EC-SOD in human aorta, LAD, and saphenous veins was studied by means of immunohistochemistry in samples from several individuals. The staining of all the samples was essentially identical. A result with a thoracic aorta specimen is presented as an example (see the Figure). EC-SOD is apparently evenly distributed throughout the wall, with significant amounts observed in all layers.

View larger version (20K): [in this window] [in a new window]   Figure 1. Immunostaining of EC-SOD in nondiseased thoracic aorta from a 40-year-old man, collected 48 hours postmortem. The anti–EC-SOD antibody used (1.4 mg/L) (A) was raised against the recombinant enzyme in rabbit. Nonimmunized rabbit IgG was used as a negative control (2.4 mg/L) (B). e indicates endothelium; i, intima; m, media; and a, adventitia. The upper pair of arrows mark the internal elastic lamina; the lower pair, the border between media and adventitia. Bar=200 µm.

SOD Isoenzymes in Aorta From Various Mammalian Species
We have previously found that the EC-SOD content of tissues shows a considerable interspecies variation, whereas the contents of CuZn-SOD and Mn-SOD vary to a lesser extent.²⁴ To investigate whether these differences also occur in blood vessels, we measured the levels of the SOD isoenzymes in the aortas from seven additional mammalian species (Table 2). We find a remarkable variation in the EC-SOD content, whereas the differences in CuZn-SOD activity are relatively small. The Mn-SOD activity displays an intermediate variation among the species.

View this table: [in this window] [in a new window]   Table 2. SOD Isoenzymes in Aorta From Various Mammals

Sources of EC-SOD in the Vascular Wall
Although the intracellular isoenzymes CuZn-SOD and Mn-SOD occur in all nucleated cell types, EC-SOD is expressed by only a few.²⁵ Expression by fibroblasts and glia cells has been demonstrated before, whereas other cell lines, eg, endothelial cells (n=6), lacked expression.²⁵ All investigated suspension-growing cell lines of hematological origin likewise lacked expression. To further explore potential sources of EC-SOD in the vascular wall, expression by arterial smooth muscle cells was examined (Table 3). The smooth muscle cell lines all secreted EC-SOD in large amounts, similar to those previously found for fibroblast cell lines. Since smooth muscle cells constitute the major portion of the cells occurring in the vascular wall, they should be the principal source of the EC-SOD existing in this location.

View this table: [in this window] [in a new window]   Table 3. Expression of EC-SOD by Cultured Human Smooth Muscle Cells

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The major finding of the present study is the exceptionally high EC-SOD content in the extracellular space of the human arterial wall. The CuZn-SOD and Mn-SOD contents are relatively low. The cell densities of the vascular walls are low, however, and a comparison with other tissues on the basis of U/mg DNA²⁶ indicates that the average content per cell of these intracellular isoenzymes is normal or slightly high. The present study, however, provides no information on the distribution of these intracellular isoenzymes among the various cell types in the vascular wall. Since the superoxide anion radical crosses membranes poorly,²⁷ the SOD isoenzymes exert their protective functions in their distinct compartments. For these reasons, we focus this discussion on EC-SOD and events in the vascular wall extracellular space.

The present (Table 3) and previous²⁵ analyses of EC-SOD expression by human cell lines indicate that the principal source of the enzyme in the vascular wall is the smooth muscle cells. EC-SOD shows high affinity for heparin and some related sulfated glycosaminoglycans^{28 29} and exists, in tissues, reversibly anchored primarily to heparan sulfate proteoglycans in the interstitial matrix and on cell surfaces.^{30 31} After secretion, the EC-SOD should slowly diffuse in the vascular wall and distribute itself according to amount and affinity of the glycosaminoglycans occurring in the various microenvironments. This process seems to result in a relatively even distribution of the enzyme to the various layers of the vessel wall (Figure). Assuming a distribution volume of 30% in the arterial wall, an average EC-SOD activity of 15 000 to 20 000 U/mL in the extracellular space can be estimated. CuZn-SOD, which is commercially available and has been widely used in similar studies, has an equivalent activity equal to 110 mg/L CuZn-SOD. The very high EC-SOD activity in the arterial interstitium, including the intima, could be important for the suppression of various pathological processes.

LDL oxidation has been suggested to be a primary step in atherogenesis.³² In several in vitro models of LDL oxidation, addition of CuZn-SOD has been shown to be protective,^{2 3 4 5 6} suggesting a potential involvement of the superoxide radical in the process in vivo. The high EC-SOD activity in the human arterial intima should effectively suppress any direct involvement of the superoxide radical in LDL oxidation.

NO· produced by the endothelium is a major physiological vasodilator.^{33 34} It also reduces the adhesion of platelets³⁵ and leukocytes³⁶ to the vascular wall and by terminating lipid peroxidation may protect LDL from oxidation.^{37 38} Nitric oxide synthase can also be induced in phagocytic cells and smooth muscle cells.³⁹ NO· reacts with superoxide at an essentially diffusion-limited rate to form the very toxic compound peroxynitrite.^{6 7} Peroxynitrite, which is in itself an oxidizing agent, may nitrate proteins⁸ and induce LDL oxidation¹⁰ and may decompose to other strongly oxidizing species.⁹ Thus, the interaction between superoxide and NO· reduces the physiological and protective effects of NO· and leads to the formation of toxic compounds. The extensive nitration of protein tyrosines found in human atherosclerotic lesions shows that significant amounts of peroxynitrite may be formed under pathological conditions in vivo.⁴⁰ With maximal stimulation of the endothelium of isolated rabbit aorta, NO· concentrations of 0.85 µmol/L have been measured in the wall,⁴¹ although in vivo the concentrations may be lower due to scavenging of NO· by hemoglobin.⁴² With the high rate constant for peroxynitrite formation, 6.7x10⁹ L·mol^-1·s^-1,⁷ it can be calculated that on the order of 19 000 U/mL (EC)SOD is needed to compete equally with 0.85 µmol/L NO· for superoxide radicals. Thus, the high EC-SOD activity in the human arterial wall interstitium should be sufficient to compete with basal concentrations of NO· but may allow significant formation of peroxynitrite under maximal agonist stimulation of the endothelium and when NO synthase is induced in other cell types. In several pathological situations the rate of superoxide formation is also increased in the arterial wall^{43 44 45 46 47} and may equal or exceed the rate of NO· formation, as indicated by the effects of administration of large amounts of SOD on NO·-induced responses. Thus, the injection of a heparan sulfate–binding SOD derivative reduced the blood pressure in spontaneously hypertensive rats,⁴³ addition of SOD enhanced acetylcholine-induced relaxation of aortas from diabetic rats,⁴⁴ and in vivo administration of liposome-encapsulated CuZn-SOD enhanced the response to acetylcholine of isolated aortic rings derived from cholesterol-fed rabbits.⁴⁵ All these studies were performed on species with less arterial wall EC-SOD than is found in humans, and the results emphasize the potential protective role of a high EC-SOD level of the arterial wall interstitium.

We have previously found considerable differences among mammalian species in organ EC-SOD contents.²⁴ Here we describe large differences in the levels in the aortic wall. One similarity among the species is that in all cases except rats and mice the arterial wall contains by far the largest amounts of EC-SOD of all organs analyzed, suggesting a particularly important role for the enzyme in this tissue. The rat species deviates from all other mammals in that the organ EC-SOD content is very low, but the plasma content is relatively high.²⁴ Unlike the EC-SOD of other species, rat EC-SOD is dimeric and has a low affinity for heparin and does not bind to heparan sulfate under physiological conditions.⁴⁸ In the mouse, the lungs and the aorta contain equally large amounts of EC-SOD. The wide interspecies differences indicate that the pathophysiological effects of superoxide radicals in the vascular wall should differ among species. In support of this suggestion we have shown that preincubation of rabbit aortic rings with recombinant human EC-SOD results in significant protection of NO·-mediated relaxation against superoxide formed by pyrogallol autoxidation.⁴⁹ The preincubation of the rabbit aortic rings resulted in a rise in (EC)SOD activity of about 5000 U/g wet weight, ie, to reach the levels of the human aorta. Thus, the difference in EC-SOD levels among species is an important factor to consider when extrapolating experimental findings in animal models to the situation in humans.

In summary, the very high EC-SOD activity of the human arterial wall interstitium and the large differences among mammalian species deserve attention in all studies on vascular wall pathology potentially involving oxidative stress.

	Selected Abbreviations and Acronyms

 

CuZn-SOD = copper-and-zinc–containing SOD EC-SOD = extracellular superoxide dismutase LAD = left anterior descending coronary artery Mn-SOD = manganese-containing SOD NO· = nitric oxide SOD = superoxide dismutase

	Acknowledgments

 
This study was supported by the Swedish Natural Science Research Council, grant 9204. The authors would like to thank Agneta Öberg, Eva Bern, and Els-Marie Öhman for their skillful technical assistance.

Received March 10, 1995; accepted August 25, 1995.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Mehta JL, Lawson DL, Nichols WW. Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A. Am J Physiol. 1989;257:H1240-H1246. [Abstract/Free Full Text]

2. Steinbrecher UP, Zhang H, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med. 1990;9:155-168. [Medline] [Order article via Infotrieve]

3. Heinecke JW, Baker L, Rosen H, Chait A. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest. 1986;77:757-761.

4. Kawamura M, Heinecke JW, Chait A. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. J Clin Invest. 1994;94:771-778.

5. Heinecke JW, Kawamura M, Suzuki L, Chait A. Oxidation of low density lipoprotein by thiols: superoxide-dependent and -independent mechanisms. J Lipid Res. 1993;34:2051-2061. [Abstract]

6. Beckman JS, Beckman T, Chen J, Marshall PA, Freeman B. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990;87:1620-1624. [Abstract/Free Full Text]

7. Huie TE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun.. 1993;18:195-199. [Medline] [Order article via Infotrieve]

8. Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992;298:431-437. [Medline] [Order article via Infotrieve]

9. Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beckman JS. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol. 1992;5:834-842. [Medline] [Order article via Infotrieve]

10. Darley-Usmar VM, Hogg N, O'Leary VJ, Wilson MT, Moncada S. The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein. Free Radic Res Commun.. 1992;17:9-20. [Medline] [Order article via Infotrieve]

11. Katusic ZS, Vanhoutte PM. Superoxide anion is an endothelium-derived contracting factor. Am J Physiol. 1989;257:H33-H37. [Abstract/Free Full Text]

12. Marklund SL. Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci U S A. 1982;79:7634-7638. [Abstract/Free Full Text]

13. McCord JM, Fridovich I. Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244:6049-6055. [Abstract/Free Full Text]

14. Weisiger RA, Fridovich I. Mitochondrial superoxide dismutase: site of synthesis and intramitochondrial localization. J Biol Chem. 1973;248:4793-4796. [Abstract/Free Full Text]

15. Marklund SL. Spectrophotometric study of spontaneous disproportionation of superoxide anion radical and sensitive direct assay for superoxide dismutase. J Biol Chem. 1976;251:7504-7507. [Free Full Text]

16. Marklund SL. Direct assay of superoxide dismutase with potassium superoxide. In: Greenwald RA, ed. Handbook of Methods for Oxygen Radical Research. Boca Raton, Fla: CRC Press Inc; 1985:249-255.

17. Karlsson K, Marklund SL. Plasma clearance of human extracellular superoxide dismutase C in rabbits. J Clin Invest. 1988;82:762-766.

18. Tibell L, Hjalmarsson K, Edlund T, Skogman G, Engström Å, Marklund SL. Expression of human extracellular superoxide dismutase in Chinese hamster ovary cells and characterization of the product. Proc Natl Acad Sci U S A. 1987;84:6634-6638. [Abstract/Free Full Text]

19. Marklund SL. Extracellular superoxide dismutase in human tissues and human cell lines. J Clin Invest. 1984;74:1398-1403.

20. Bradford MM. A rapid and sensitive method for the quantitation of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254. [Medline] [Order article via Infotrieve]

21. Labarca C, Paigen K. A simple, rapid and sensitive DNA assay procedure. Anal Biochem. 1980;102:344-352. [Medline] [Order article via Infotrieve]

22. Fager G, Hansson GK, Ottosson P, Dahllöf B, Bondjers G. Human arterial smooth muscle cells in culture: effects of platelet-derived growth factor and heparin on growth in vitro. Exp Cell Res. 1988;176:319-335. [Medline] [Order article via Infotrieve]

23. Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Biol Chem. 1986;103:2787-2796.

24. Marklund SL. Extracellular superoxide dismutase and other superoxide dismutase isoenzymes in tissues from nine mammalian species. Biochem J. 1984;222:649-655. [Medline] [Order article via Infotrieve]

25. Marklund SL. Expression of extracellular superoxide dismutase by human cell lines. Biochem J. 1990;266:213-219. [Medline] [Order article via Infotrieve]

26. Sandström JS, Karlsson K, Edlund T, Marklund SL. Heparin-affinity patterns and composition of extracellular superoxide dismutase in human plasma and tissues. Biochem J. 1993;294:853-857.

27. Winterbourn CC, Stern A. Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical. J Clin Invest. 1987;80:1486-1491.

28. Sandström J, Carlsson L, Marklund SL, Edlund T. The heparin-binding domain of extracellular superoxide dismutase, and formation of variants with reduced heparin affinity. J Biol Chem. 1992;267:18205-18209. [Abstract/Free Full Text]

29. Karlsson K, Lindahl U, Marklund SL. Binding of human extracellular superoxide dismutase C to sulphated glycosaminoglycans. Biochem J. 1988;256:29-33. [Medline] [Order article via Infotrieve]

30. Karlsson K, Marklund SL. Binding of human extracellular superoxide dismutase C to cultured cell lines and to blood cells. Lab Invest. 1989;60:659-666. [Medline] [Order article via Infotrieve]

31. Karlsson K, Sandström J, Edlund A, Marklund SL. Turnover of extracellular superoxide dismutase in tissues. Lab Invest. 1994;70:705-710. [Medline] [Order article via Infotrieve]

32. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915-924. [Medline] [Order article via Infotrieve]

33. Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524-526. [Medline] [Order article via Infotrieve]

34. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265-9269. [Abstract/Free Full Text]

35. Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987;2:1057-1058. [Medline] [Order article via Infotrieve]

36. Gaboury J, Woodman RC, Granger DN, Reinhardt P, Kubes P. Nitric oxide prevents leukocyte adherence: role of superoxide. Am J Physiol. 1993;265:H862-H867. [Abstract/Free Full Text]

37. Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S. Inhibition of low-density lipoprotein oxidation by nitric oxide: potential role in atherogenesis. FEBS Lett. 1993;334:170-174. [Medline] [Order article via Infotrieve]

38. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation: formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 1994;269:26066-26075. [Abstract/Free Full Text]

39. Beasley D, Schwartz JH, Brenner BM. Interleukin 1 induces prolonged l-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest. 1991;87:602-608.

40. Beckman JS, Yao ZY, Anderson PG, Chen J, Accavitti MA, Tarpey MM, White CR. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994;175:81-88.

41. Malinski T, Taha Z, Grunfeld S, Pattou S, Kapturczak M, Tomboulian P. Diffusion of nitric oxide in the aorta wall monitored in situ by porphyrinic microsensors. Biochem Biophys Res Commun.. 1993;193:1076-1082. [Medline] [Order article via Infotrieve]

42. Lancaster JR. Simulation of the diffusion and reaction of endogenously produced nitric oxide. Proc Natl Acad Sci U S A. 1994;91:8137-8148. [Abstract/Free Full Text]

43. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A. 1991;88:10045-10048. [Abstract/Free Full Text]

44. Hattori Y, Kawasaki H, Abe K, Kanno M. Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta. Am J Physiol. 1991;261:H1086-H1094. [Abstract/Free Full Text]

45. White RC, Brock TA, Chang LY, Crapo J, Briscoe P, Ku D, Bradley WA, Gianturco SH, Gore J, Freeman BA, Tarpey MM. Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci U S A. 1994;91:1044-1048. [Abstract/Free Full Text]

46. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest. 1993;91:2546-2551.

47. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance. J Clin Invest. 1995;95:187-194.

48. Karlsson K, Marklund SL. Extracellular superoxide dismutase in the vascular system of mammals. Biochem J. 1988;255:223-228. [Medline] [Order article via Infotrieve]

49. Abrahamsson T, Brandt U, Marklund SL, Sjöquist PO. Vascular bound recombinant extracellular superoxide dismutase type C protects against the detrimental effects of superoxide radicals on endothelium-dependent arterial relaxation. Circ Res. 1992;70:264-271.[Abstract/Free Full Text]

This article has been cited by other articles:

				R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2008; 13(4): 279 - 297. [Abstract] [PDF]

				M. C. Gongora, H. E. Lob, U. Landmesser, T. J. Guzik, W. D. Martin, K. Ozumi, S. M. Wall, D. S. Wilson, N. Murthy, M. Gravanis, et al. Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air: A Potential Mechanism Underlying Adult Respiratory Distress Syndrome Am. J. Pathol., October 1, 2008; 173(4): 915 - 926. [Abstract] [Full Text] [PDF]

				M. Liao, Z. Liu, J. Bao, Z. Zhao, J. Hu, X. Feng, R. Feng, Q. Lu, Z. Mei, Y. Liu, et al. A proteomic study of the aortic media in human thoracic aortic dissection: Implication for oxidative stress J. Thorac. Cardiovasc. Surg., July 1, 2008; 136(1): 65 - 72. [Abstract] [Full Text] [PDF]

				H. Alcaino, D. Greig, M. Chiong, H. Verdejo, R. Miranda, R. Concepcion, J. L. Vukasovic, G. Diaz-Araya, R. Mellado, L. Garcia, et al. Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure Eur J Heart Fail, July 1, 2008; 10(7): 646 - 651. [Abstract] [Full Text] [PDF]

				F. Kamezaki, H. Tasaki, K. Yamashita, M. Tsutsui, S. Koide, S. Nakata, A. Tanimoto, M. Okazaki, Y. Sasaguri, T. Adachi, et al. Gene Transfer of Extracellular Superoxide Dismutase Ameliorates Pulmonary Hypertension in Rats Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 219 - 226. [Abstract] [Full Text] [PDF]

				H. W. Kim, A. Lin, R. E. Guldberg, M. Ushio-Fukai, and T. Fukai Essential Role of Extracellular SOD in Reparative Neovascularization Induced by Hindlimb Ischemia Circ. Res., August 17, 2007; 101(4): 409 - 419. [Abstract] [Full Text] [PDF]

				O. Jung, S. L. Marklund, N. Xia, R. Busse, and R. P. Brandes Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 470 - 477. [Abstract] [Full Text] [PDF]

				T. Szasz, K. Thakali, G. D. Fink, and S. W. Watts A Comparison of Arteries and Veins in Oxidative Stress: Producers, Destroyers, Function, and Disease Experimental Biology and Medicine, January 1, 2007; 232(1): 27 - 37. [Abstract] [Full Text] [PDF]

				J. Kitayama, C. Yi, F. M. Faraci, and D. D. Heistad Modulation of Dilator Responses of Cerebral Arterioles by Extracellular Superoxide Dismutase Stroke, November 1, 2006; 37(11): 2802 - 2806. [Abstract] [Full Text] [PDF]

				W. J. Welch, T. Chabrashvili, G. Solis, Y. Chen, P. S. Gill, S. Aslam, X. Wang, H. Ji, K. Sandberg, P. Jose, et al. Role of Extracellular Superoxide Dismutase in the Mouse Angiotensin Slow Pressor Response Hypertension, November 1, 2006; 48(5): 934 - 941. [Abstract] [Full Text] [PDF]

				Y. Chu, R. Piper, S. Richardson, Y. Watanabe, P. Patel, and D. D. Heistad Endocytosis of Extracellular Superoxide Dismutase Into Endothelial Cells: Role of the Heparin-Binding Domain Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 1985 - 1990. [Abstract] [Full Text] [PDF]

				M. C. Gongora, Z. Qin, K. Laude, H. W. Kim, L. McCann, J. R. Folz, S. Dikalov, T. Fukai, and D. G. Harrison Role of Extracellular Superoxide Dismutase in Hypertension Hypertension, September 1, 2006; 48(3): 473 - 481. [Abstract] [Full Text] [PDF]

				S. Iida, Y. Chu, R. M. Weiss, Y. M. Kang, F. M. Faraci, and D. D. Heistad Vascular effects of a common gene variant of extracellular superoxide dismutase in heart failure Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H914 - H920. [Abstract] [Full Text] [PDF]

				G. L. Baumbach, S. P. Didion, and F. M. Faraci Hypertrophy of Cerebral Arterioles in Mice Deficient in Expression of the Gene for CuZn Superoxide Dismutase Stroke, July 1, 2006; 37(7): 1850 - 1855. [Abstract] [Full Text] [PDF]

				N. Ardanaz and P. J. Pagano Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Experimental Biology and Medicine, March 1, 2006; 231(3): 237 - 251. [Abstract] [Full Text] [PDF]

				Y. Chu, A. Alwahdani, S. Iida, D. D. Lund, F. M. Faraci, and D. D. Heistad Vascular Effects of the Human Extracellular Superoxide Dismutase R213G Variant Circulation, August 16, 2005; 112(7): 1047 - 1053. [Abstract] [Full Text] [PDF]

				S. Iida, Y. Chu, J. Francis, R. M. Weiss, C. A. Gunnett, F. M. Faraci, and D. D. Heistad Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H525 - H532. [Abstract] [Full Text] [PDF]

				S. Turkseven, A. Kruger, C. J. Mingone, P. Kaminski, M. Inaba, L. F. Rodella, S. Ikehara, M. S. Wolin, and N. G. Abraham Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H701 - H707. [Abstract] [Full Text] [PDF]

				J. A. Leopold and J. Loscalzo Oxidative Enzymopathies and Vascular Disease Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1332 - 1340. [Abstract] [Full Text] [PDF]

				J. W. Park, W.-N. Qi, Y. Cai, I. Zelko, J. Q. Liu, L.-E. Chen, J. R. Urbaniak, and R. J. Folz Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H181 - H187. [Abstract] [Full Text] [PDF]

				U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al. Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans Circulation, May 10, 2005; 111(18): 2356 - 2363. [Abstract] [Full Text] [PDF]

				V. Jeney, S. Itoh, M. Wendt, Q. Gradek, M. Ushio-Fukai, D. G. Harrison, and T. Fukai Role of Antioxidant-1 in Extracellular Superoxide Dismutase Function and Expression Circ. Res., April 15, 2005; 96(7): 723 - 729. [Abstract] [Full Text] [PDF]

				A. D. Nguyen, S. Itoh, V. Jeney, H. Yanagisawa, M. Fujimoto, M. Ushio-Fukai, and T. Fukai Fibulin-5 Is a Novel Binding Protein for Extracellular Superoxide Dismutase Circ. Res., November 26, 2004; 95(11): 1067 - 1074. [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]

				J. J. Andresen, F. M. Faraci, and D. D. Heistad Vasomotor responses in MnSOD-deficient mice Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1141 - H1148. [Abstract] [Full Text] [PDF]

				L. B. Mamo, H. B. Suliman, B.-L. Giles, R. L. Auten, C. A. Piantadosi, and E. Nozik-Grayck Discordant Extracellular Superoxide Dismutase Expression and Activity in Neonatal Hyperoxic Lung Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 313 - 318. [Abstract] [Full Text] [PDF]

				F. M. Faraci and S. P. Didion Vascular Protection: Superoxide Dismutase Isoforms in the Vessel Wall Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1367 - 1373. [Abstract] [Full Text] [PDF]

				M. C. Zimmerman, E. Lazartigues, R. V. Sharma, and R. L. Davisson Hypertension Caused by Angiotensin II Infusion Involves Increased Superoxide Production in the Central Nervous System Circ. Res., July 23, 2004; 95(2): 210 - 216. [Abstract] [Full Text] [PDF]

				J. Widder, T. Behr, D. Fraccarollo, K. Hu, P. Galuppo, P. Tas, C. E Angermann, G. Ertl, and J. Bauersachs Vascular endothelial dysfunction and superoxide anion production in heart failure are p38 MAP kinase-dependent Cardiovasc Res, July 1, 2004; 63(1): 161 - 167. [Abstract] [Full Text] [PDF]

				U. Landmesser, B. Hornig, and H. Drexler Endothelial Function: A Critical Determinant in Atherosclerosis? Circulation, June 1, 2004; 109(21_suppl_1): II-27 - II-33. [Abstract] [Full Text] [PDF]

				K. Juul, A. Tybjaerg-Hansen, S. Marklund, N. H.H. Heegaard, R. Steffensen, H. Sillesen, G. Jensen, and B. G. Nordestgaard Genetically Reduced Antioxidative Protection and Increased Ischemic Heart Disease Risk: The Copenhagen City Heart Study Circulation, January 6, 2004; 109(1): 59 - 65. [Abstract] [Full Text] [PDF]

				M. Horiuchi, M. Tsutsui, H. Tasaki, T. Morishita, O. Suda, S. Nakata, S.-i. Nihei, M. Miyamoto, R. Kouzuma, M. Okazaki, et al. Upregulation of Vascular Extracellular Superoxide Dismutase in Patients With Acute Coronary Syndromes Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 106 - 111. [Abstract] [Full Text] [PDF]

				P. F. Leite, A. Danilovic, P. Moriel, K. Dantas, S. Marklund, A. P. V. Dantas, and F. R.M. Laurindo Sustained Decrease in Superoxide Dismutase Activity Underlies Constrictive Remodeling After Balloon Injury in Rabbits Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2197 - 2202. [Abstract] [Full Text] [PDF]

				B. Gao, S. C. Flores, J. A. Leff, S. K. Bose, and J. M. McCord Synthesis and anti-inflammatory activity of a chimeric recombinant superoxide dismutase: SOD2/3 Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L917 - L925. [Abstract] [Full Text] [PDF]

				F. Kimura, G. Hasegawa, H. Obayashi, T. Adachi, H. Hara, M. Ohta, M. Fukui, Y. Kitagawa, H. Park, N. Nakamura, et al. Serum Extracellular Superoxide Dismutase in Patients With Type 2 Diabetes: Relationship to the development of micro- and macrovascular complications Diabetes Care, April 1, 2003; 26(4): 1246 - 1250. [Abstract] [Full Text] [PDF]

				J. W. E. Rush, J. R. Turk, and M. H. Laughlin Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1378 - H1387. [Abstract] [Full Text] [PDF]

				Y. Chu, S. Iida, D. D. Lund, R. M. Weiss, G. F. DiBona, Y. Watanabe, F. M. Faraci, and D. D. Heistad Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain Circ. Res., March 7, 2003; 92(4): 461 - 468. [Abstract] [Full Text] [PDF]

				F. M. Faraci Vascular Protection Stroke, February 1, 2003; 34(2): 327 - 329. [Full Text] [PDF]

				U. Landmesser and H. Drexler Oxidative stress, the renin-angiotensin system, and atherosclerosis Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A3 - A7. [Abstract] [PDF]

				U. Landmesser, S. Spiekermann, S. Dikalov, H. Tatge, R. Wilke, C. Kohler, D. G. Harrison, B. Hornig, and H. Drexler Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure: Role of Xanthine-Oxidase and Extracellular Superoxide Dismutase Circulation, December 10, 2002; 106(24): 3073 - 3078. [Abstract] [Full Text] [PDF]

				I. T. Demchenko, T. D. Oury, J. D. Crapo, and C. A. Piantadosi Regulation of the Brain's Vascular Responses to Oxygen Circ. Res., November 29, 2002; 91(11): 1031 - 1037. [Abstract] [Full Text] [PDF]

				S. P. Didion, M. J. Ryan, L. A. Didion, P. E. Fegan, C. D. Sigmund, and F. M. Faraci Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice Circ. Res., November 15, 2002; 91(10): 938 - 944. [Abstract] [Full Text] [PDF]

				A. Zalewski, Y. Shi, and A. G. Johnson Diverse Origin of Intimal Cells: Smooth Muscle Cells, Myofibroblasts, Fibroblasts, and Beyond? Circ. Res., October 18, 2002; 91(8): 652 - 655. [Full Text] [PDF]

				M. O. Laukkanen, A. Kivela, T. Rissanen, J. Rutanen, M. K. Karkkainen, O. Leppanen, J. H. Brasen, and S. Yla-Herttuala Adenovirus-Mediated Extracellular Superoxide Dismutase Gene Therapy Reduces Neointima Formation in Balloon-Denuded Rabbit Aorta Circulation, October 8, 2002; 106(15): 1999 - 2003. [Abstract] [Full Text] [PDF]

				U. Landmesser and H. Drexler Toward Understanding of Extracellular Superoxide Dismutase Regulation in Atherosclerosis: A Novel Role of Uric Acid? Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1367 - 1368. [Full Text] [PDF]

				M. J. McGirt, A. Parra, H. Sheng, Y. Higuchi, T. D. Oury, D. T. Laskowitz, R. D. Pearlstein, and D. S. Warner Attenuation of Cerebral Vasospasm After Subarachnoid Hemorrhage in Mice Overexpressing Extracellular Superoxide Dismutase Stroke, September 1, 2002; 33(9): 2317 - 2323. [Abstract] [Full Text] [PDF]

				H. U. Hink, N. Santanam, S. Dikalov, L. McCann, A. D. Nguyen, S. Parthasarathy, D. G. Harrison, and T. Fukai Peroxidase Properties of Extracellular Superoxide Dismutase: Role of Uric Acid in Modulating In Vivo Activity Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1402 - 1408. [Abstract] [Full Text] [PDF]

				R. Maas, E. Schwedhelm, J. Albsmeier, and R. H Boger The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function Vascular Medicine, August 1, 2002; 7(3): 213 - 225. [Abstract] [PDF]

				T. Fukai, R. J Folz, U. Landmesser, and D. G Harrison Extracellular superoxide dismutase and cardiovascular disease Cardiovasc Res, August 1, 2002; 55(2): 239 - 249. [Abstract] [Full Text] [PDF]

				M. T Gewaltig and G. Kojda Vasoprotection by nitric oxide: mechanisms and therapeutic potential Cardiovasc Res, August 1, 2002; 55(2): 250 - 260. [Abstract] [Full Text] [PDF]

				M. Rathaus and J. Bernheim Oxygen species in the microvascular environment: regulation of vascular tone and the development of hypertension Nephrol. Dial. Transplant., February 1, 2002; 17(2): 216 - 221. [Abstract] [Full Text] [PDF]

				H.U. HINK and T. FUKAI Extracellular Superoxide Dismutase, Uric Acid, and Atherosclerosis Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 483 - 490. [Abstract] [PDF]

				P. Stralin and S. L. Marklund Vasoactive factors and growth factors alter vascular smooth muscle cell EC-SOD expression Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1621 - H1629. [Abstract] [Full Text] [PDF]

				S. P. Didion, C. A. Hathaway, and F. M. Faraci Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1697 - H1703. [Abstract] [Full Text] [PDF]

				J. H. Indik, S. Goldman, and M. A. Gaballa Oxidative stress contributes to vascular endothelial dysfunction in heart failure Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1767 - H1770. [Abstract] [Full Text] [PDF]

				M.-L. Sentman, T. Brannstrom, S. Westerlund, M. O. Laukkanen, S. Yla-Herttuala, S. Basu, and S. L. Marklund Extracellular Superoxide Dismutase Deficiency and Atherosclerosis in Mice Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1477 - 1482. [Abstract] [Full Text] [PDF]

				Y. Shi, S. Patel, K. L. Davenpeck, R. Niculescu, E. Rodriguez, M. G. Magno, M. L. Ormont, J. D. Mannion, and A. Zalewski Oxidative Stress and Lipid Retention in Vascular Grafts : Comparison Between Venous and Arterial Conduits Circulation, May 15, 2001; 103(19): 2408 - 2413. [Abstract] [Full Text] [PDF]

				B. Hornig, U. Landmesser, C. Kohler, D. Ahlersmann, S. Spiekermann, A. Christoph, H. Tatge, and H. Drexler Comparative Effect of ACE Inhibition and Angiotensin II Type 1 Receptor Antagonism on Bioavailability of Nitric Oxide in Patients With Coronary Artery Disease : Role of Superoxide Dismutase Circulation, February 13, 2001; 103(6): 799 - 805. [Abstract] [Full Text] [PDF]

				H. Nakane, Y. Chu, F. M. Faraci, L. W. Oberley, D. D. Heistad, and P. H. Chan Gene Transfer of Extracellular Superoxide Dismutase Increases Superoxide Dismutase Activity in Cerebrospinal Fluid Editorial Comment Stroke, January 1, 2001; 32(1): 184 - 189. [Abstract] [Full Text] [PDF]

				E. Nozik-Grayck, C. S. Dieterle, C. A. Piantadosi, J. J. Enghild, and T. D. Oury Secretion of extracellular superoxide dismutase in neonatal lungs Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L977 - L984. [Abstract] [Full Text] [PDF]

				J. W. E. Rush, M. H. Laughlin, C. R. Woodman, and E. M. Price SOD-1 expression in pig coronary arterioles is increased by exercise training Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2068 - H2076. [Abstract] [Full Text] [PDF]

				U. Landmesser, R. Merten, S. Spiekermann, K. Buttner, H. Drexler, and B. Hornig Vascular Extracellular Superoxide Dismutase Activity in Patients With Coronary Artery Disease : Relation to Endothelium-Dependent Vasodilation Circulation, May 16, 2000; 101(19): 2264 - 2270. [Abstract] [Full Text] [PDF]

				M. C. Mahaney, S. A. Czerwinski, T. Adachi, D. E. L. Wilcken, and X. L. Wang Plasma Levels of Extracellular Superoxide Dismutase in an Australian Population : Genetic Contribution to Normal Variation and Correlations With Plasma Nitric Oxide and Apolipoprotein A-I Levels Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 683 - 688. [Abstract] [Full Text] [PDF]

				S. Patel, Y. Shi, R. Niculescu, E. H. Chung, J. L. Martin, and A. Zalewski Characteristics of Coronary Smooth Muscle Cells and Adventitial Fibroblasts Circulation, February 8, 2000; 101(5): 524 - 532. [Abstract] [Full Text] [PDF]

				P. J. Pagano, M. C. Griswold, S. Najibi, S. L. Marklund, and R. A. Cohen Resistance of endothelium-dependent relaxation to elevation of O-2 levels in rabbit carotid artery Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H2109 - H2114. [Abstract] [Full Text] [PDF]

				M. O. Laukkanen, S. Mannermaa, M. O. Hiltunen, S. Aittomaki, K. Airenne, J. Janne, and S. Yla-Herttuala Local Hypomethylation in Atherosclerosis Found in Rabbit ec-sod Gene Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2171 - 2178. [Abstract] [Full Text] [PDF]

				T. Fukai, M. R. Siegfried, M. Ushio-Fukai, K. K. Griendling, and D. G. Harrison Modulation of Extracellular Superoxide Dismutase Expression by Angiotensin II and Hypertension Circ. Res., July 9, 1999; 85(1): 23 - 28. [Abstract] [Full Text] [PDF]

				J. J. Enghild, I. B. Thogersen, T. D. Oury, Z. Valnickova, P. Hojrup, and J. D. Crapo The Heparin-binding Domain of Extracellular Superoxide Dismutase Is Proteolytically Processed Intracellularly during Biosynthesis J. Biol. Chem., May 21, 1999; 274(21): 14818 - 14822. [Abstract] [Full Text] [PDF]

				X. L. Wang, T. Adachi, A. S. Sim, and D. E. L. Wilcken Plasma Extracellular Superoxide Dismutase Levels in an Australian Population With Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., December 1, 1998; 18(12): 1915 - 1921. [Abstract] [Full Text] [PDF]

				E. P. Chen, H. B. Bittner, R. D. Davis, P. V. Trigt, and R. J. Folz Physiologic Effects Of Extracellular Superoxide Dismutase Transgene Overexpression On Myocardial Function After Ischemia And Reperfusion Injury J. Thorac. Cardiovasc. Surg., February 1, 1998; 115(2): 450 - 454. [Abstract] [Full Text] [PDF]

				J. S. Luoma, P. Stralin, S. L. Marklund, T. P. Hiltunen, T. Sarkioja, and S. Yla-Herttuala Expression of Extracellular SOD and iNOS in Macrophages and Smooth Muscle Cells in Human and Rabbit Atherosclerotic Lesions : Colocalization With Epitopes Characteristic of Oxidized LDL and Peroxynitrite-Modified Proteins Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 157 - 167. [Abstract] [Full Text] [PDF]

				S. Dikalov, B. Fink, M. Skatchkov, O. Sommer, and E. Bassenge Formation of Reactive Oxygen Species in Various Vascular Cells During Glyceryltrinitrate Metabolism Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(1): 51 - 61. [Abstract] [PDF]

				F. M. FARACI and D. D. HEISTAD Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels Physiol Rev, January 1, 1998; 78(1): 53 - 97. [Abstract] [Full Text] [PDF]

				M. Barton, F. Cosentino, R. P. Brandes, P. Moreau, S. Shaw, and T. F. Luscher Anatomic Heterogeneity of Vascular Aging : Role of Nitric Oxide and Endothelin Hypertension, October 1, 1997; 30(4): 817 - 824. [Abstract] [Full Text]

				D. L. Tribble, E. L. Gong, C. Leeuwenburgh, J. W. Heinecke, E. L. Carlson, J. G. Verstuyft, and C. J. Epstein Fatty Streak Formation in Fat-Fed Mice Expressing Human Copper-Zinc Superoxide Dismutase Arterioscler. Thromb. Vasc. Biol., September 1, 1997; 17(9): 1734 - 1740. [Abstract] [Full Text]

This Article Abstract Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strålin, P. Articles by Marklund, S. L. Search for Related Content PubMed PubMed Citation Articles by Strålin, P. Articles by Marklund, S. L. Pubmed/NCBI databases Substance via MeSH