Advertisement

Heparin-released extracellular superoxide dismutase is reduced in patients with coronary artery atherosclerosis

      Abstract

      Objectives

      We studied whether the amount of heparin-released extracellular superoxide dismutase (EC-SOD), which is an antioxidative enzyme, is associated with coronary artery disease (CAD).

      Methods and results

      EC-SOD was measured in plasma at basal and at post-heparin injection in 315 patients. Heparin-released EC-SOD was calculated as the difference between the two values. After exclusion of a mutant EC-SOD group (n = 27:8.6%), 288 patients were divided into three groups by angiographic findings; those with normal coronary (the normal group; n = 63), those with atherosclerosis without significant stenosis (the mild atherosclerosis group; n = 36), and those with significant stenosis (the atherosclerosis group; n = 189). Although the basal values were similar among the three groups, heparin-released EC-SOD levels were significantly lower in the atherosclerosis group (131.0 ± 42.8 ng/ml, p = 0.0003) than in the normal group (156.9 ± 66.2 ng/ml). Moreover, logistic analysis revealed that heparin-released EC-SOD independently contributed to CAD. The coronary score showed a significant correlation with heparin-released EC-SOD. As for factors affecting the level of heparin-released EC-SOD, the level of high-density lipoprotein cholesterol and age showed a positive correlation.

      Conclusions

      The results suggest that heparin-released EC-SOD is significantly reduced in CAD and that the tissue-bound location of this enzyme might be important for antioxidative function.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cai H.
        • Harrison D.G.
        Endothelial dysfunction in cardiovascular diseases—the role of oxidant stress.
        Cir Res. 2000; 87: 840-844
        • Gryglewski R.J.
        • Palmer R.M.J.
        • Moncada S.
        Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor.
        Nature. 1986; 320: 454-456
        • White C.R.
        • Brock T.A.
        • Chang L.Y.
        • et al.
        Superoxide and peroxynitrite in atherosclerosis.
        Proc Nat Acad Sci USA. 1994; 91: 1044-1048
        • Marklund S.L.
        Human copper-containing superoxide dismutase of high molecular weight.
        Proc Nat Acad Sci USA. 1982; 79: 7634-7638
        • Marklund S.L.
        Extracellular superoxide dismutase in human tissue and human cell lines.
        J Clin Invest. 1984; 74: 1398-1403
        • Karsson K.
        • Marklund S.L.
        Heparin-induced release of extracellular superoxide dismutase to human blood plasma.
        Biochem J. 1987; 242: 55-59
        • Marklund S.L.
        Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isohyets in fibroblast.
        J Biol Chem. 1992; 267: 6696-6701
        • Sterling P.
        • Karlsson K.
        • Johansson B.O.
        • Marklund S.L.
        The interstitial of the human arterial wall contains very large amounts of extracellular superoxide dismutase.
        Arterioscler Thromb Vasc Biol. 1995; 15: 2032-2036
        • Oury T.D.
        • Day B.J.
        • Crapo J.D.
        Extracellular superoxide dismutase in vessels and airways of humans and baboons.
        Free Radic Biol Med. 1996; 20: 957-965
        • Oury T.D.
        • Day B.J.
        • Crapo J.D.
        Extracellular superoxide dismutase: a regulator of nitric oxide bioavailability.
        Lab Invest. 1996; 75: 617-636
        • Fukai T.
        • Galis Z.S.
        • Meng X.P.
        • Parthasarathy S.
        • Harrison D.G.
        Vascular expression of extracellular superoxide dismutase in atherosclerosis.
        J Clin Invest. 1998; 101: 2101-2111
        • Fukai T.
        • Folz R.J.
        • Landmesser U.
        • Harrison D.G.
        Extracellular superoxide dismutase and cardiovascular disease.
        Cardiovasc Res. 2002; 55: 239-249
        • Landmesser U.
        • Merten R.
        • Spiekermann S.
        • Buttner K.
        • Drexler H.
        • Hornig B.
        Vascular extracellular superoxide dismutase activity in patients with coronary artery disease, relation to endothelium-dependent vasodilation.
        Circulation. 2000; 101: 2264-2270
        • Juul K.
        • Tybjarg-Hansen A.
        • Marklund S.
        • et al.
        Genetically reduced antioxidative protection and increased ischemic heart disease risk—the Copenhagen city heart study.
        Circulation. 2004; 109: 59-65
        • Horiuchi M.
        • Tsutsui M.
        • Tasaki H.
        • et al.
        Upregulation of vascular extracellular superoxide dismutase in patients with acute coronary syndromes.
        Arterioscler thromb Vasc Biol. 2004; 24: 106-111
        • Adachi T.
        • Yamada H.
        • Yamada Y.
        • et al.
        Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface.
        Biochem J. 1996; 313: 235-239
        • Marklund S.L.
        • Nilsson P.
        • Israelsson K.
        • Schampi I.
        • Peltonen M.
        • Asplund K.
        Two variants of extracellular-superoxide dismutase: relationship to cardiovascular risk factors in an unselected middle-aged population.
        J Internal Med. 1997; 242: 5-14
        • Adachi T.
        • Ohta H.
        • Yamada H.
        • Futenma A.
        • Kato K.
        • Hirano K.
        Quantitative analysis of extracellular superoxide-dismutase in serum and urine by ELISA with monoclonal antibody.
        Clin Chim Acta. 1992; 212: 89-102
        • Tasaki H.
        • Nakashima Y.
        • Nandate
        • Yashiro A.
        • Kawashima T.
        • Kuroiwa A.
        Comparison of serum of lipid values in variant angina pectoris and fixed artery disease with normal subjects.
        Am J Cardiol. 1989; 63: 1441-1445
        • Wang X.L.
        • Adachi T.
        • Sim A.S.
        • Wilcken D.E.L.
        Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease.
        Arterioscler Throm Vasc Biol. 1998; 18: 1915-1921
        • Adachi T.
        • Yamada H.
        • Futenma
        • Kato K.
        • Hirano K.
        Heparin-induced release of extracellular-superoxide dismutase form (V) to plasma.
        J Biochem (Tokyo). 1995; 117: 586-590
        • Fennell J.P.
        • Brosnan M.J.
        • Frater A.J.
        • et al.
        Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelium dysfunction in a rat model of hypertension.
        Gene Ther. 2002; 9: 110-117
        • Chu Y.
        • Iida S.
        • Lund D.D.
        • et al.
        Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats—role of heparin-binding domain.
        Cir Res. 2003; 92: 461-468
        • Laukkanen M.O.
        • Kivela A.
        • Rissanen T.
        • et al.
        Adenovirus-mediated extracellular superoxide dismutase gene therapy reduces neointimal formation in balloon-denuded rabbit aorta.
        Circulation. 2002; 106: 1999-2003
        • Watanabe Y.
        • Chu Y.
        • Andresen J.J.
        • Nakane H.
        • Faraci F.
        • Heistad D.D.
        Gene transfer of extracellular superoxide dismutase reduces cerebral vasospasm after subarachoid hemorrhage.
        Stroke. 2003; 34: 434-440
        • Takatsu H.
        • Tasaki H.
        • Kim H.N.
        • et al.
        Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation.
        Biochem Biophys Res Commun. 2001; 286: 84-91
        • Leite P.F.
        • Danilovic A.
        • Moriel P.
        • et al.
        Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits.
        Arterioscler Thromb Vasc Biol. 2003; 23: 2197-2202
        • Luoma J.S.
        • Strålin P.
        • Marklund S.L.
        • Hiltunen T.P.
        • Sarkioja T.
        • Yla-Herttuala S.
        Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atheroclerotic lesions.
        Arterioscler Throm Vasc Biol. 1998; 18: 157-167
        • Droge W.
        Free radicals in the physiological control of cell function.
        Phys Rev. 2002; 82: 47-95
        • Pillarisetti S.
        Lipoprotein modulation of subendothelial heparan sulfate proteoglycan (perlecan) and atherogenicity.
        Trends Cardiovasc Med. 2000; 10: 60-65